Making Patient-Centric Immunotherapy a Reality in Lung Cancer: Best Practices for Patient Education, irAE Management, and Survivorship Care
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May 15, 2024
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About This Presentation
Co-Chairs and Presenter Marianne Davies, DNP, ACNP, AOCNP, FAAN, Beth Sandy, MSN, CRNP, FAPO, and Matthew A. Gubens, MD, MS, FASCO, discuss NSCLC in this CME/MOC/NCPD/ILNA/IPCE activity titled “Making Patient-Centric Immunotherapy a Reality in Lung Cancer: Best Practices for Patient Education, irA...
Slide Content
Making Patient-Centric Immunotherapy
a Reality in Lung Cancer
Best Practices for Patient Education,
irAE Management, and Survivorship Care
Beth Sandy, MSN, CRNP, FAPO
Thoracic Oncology Nurse Practitioner
Abramson Cancer Center
University of Pennsylvania
Philadelphia, Pennsylvania
Marianne Davies, DNP, ACNP, AOCNP, FAAN
Program Manager Care Signature, Oncology
‘Oncology Nurse Practitioner
Yale Comprehensive Cancer Center & Smilow
Cancer Center
iAssociats PIE or Matthew A. Gubens, MD, MS, FASCO
Yale School of Nursing P 4 Professor of Medicine
New Haven ¡Connecticut Medical Director, Thoracic Medical Oncology
Division of Hematology/Oncology
Department of Medicine
University of California San Francisco
San Francisco, California
Go online to access full CME/MOC/NCPD/ILNA/PCE information, including faculty disclosures.
Copyright © 2000-2024, PeerView
a Reality in Lung Cancer
Best Practices for Patient Education,
irAE Management, and Survivorship Care
Beth Sandy, MSN, CRNP, FAPO
Thoracic Oncology Nurse Practitioner
Abramson Cancer Center
University of Pennsylvania
Philadelphia, Pennsylvania
Marianne Davies, DNP, ACNP, AOCNP, FAAN
Program Manager Care Signature, Oncology
‘Oncology Nurse Practitioner
Yale Comprehensive Cancer Center & Smilow
Cancer Center
iAssociats PIE or Matthew A. Gubens, MD, MS, FASCO
Yale School of Nursing P 4 Professor of Medicine
New Haven ¡Connecticut Medical Director, Thoracic Medical Oncology
Division of Hematology/Oncology
Department of Medicine
University of California San Francisco
San Francisco, California
Go online to access full CME/MOC/NCPD/ILNA/PCE information, including faculty disclosures.
Copyright © 2000-2024, PeerView
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Our Goals for Today
Augment your knowledge of the evolving role
of immunotherapies in lung cancer
Equip you with skills to detect, assess, and manage irAEs
Provide you with guidance and resources for educating,
engaging, and supporting your patients with lung cancer
Our Goals for Today
Augment your knowledge of the evolving role
of immunotherapies in lung cancer
Equip you with skills to detect, assess, and manage irAEs
Provide you with guidance and resources for educating,
engaging, and supporting your patients with lung cancer
MasterClass 1
Navigating Immunotherapy Options
in NSCLC: How Nurses and the Care
Team Select ICls
Matthew A. Gubens, MD, MS, FASCO
Professor of Medicine
Medical Director, Thoracic Medical Oncology
Division of Hematology/Oncology
Department of Medicine
University of California San Francisco
San Francisco, California
Copyright © 2000-2024, PeerView
Navigating Immunotherapy Options
in NSCLC: How Nurses and the Care
Team Select ICls
Matthew A. Gubens, MD, MS, FASCO
Professor of Medicine
Medical Director, Thoracic Medical Oncology
Division of Hematology/Oncology
Department of Medicine
University of California San Francisco
San Francisco, California
Copyright © 2000-2024, PeerView
How Do We Choose Among
the Many Immunotherapy Options
in Advanced/Metastatic NSCLC?
the Many Immunotherapy Options
in Advanced/Metastatic NSCLC?
A Case to Consider
72-year-old man who quit smoking 35 years ago (30 pack-years) was found to have a 3.4-cm RML
mass on a coronary calcium scan
PET CT: 3.4-cm x 3.4-cm RML mass, right hilar and subcarinal adenopathy, and L1, 12th rib, and left
scapular metastases
MRI brain: negative for metastasis
Comorbidities: HTN, gout, hyperlipidemia
ECOG 0 at diagnosis
He is now noting mild left upper back pain
Pathology: EBUS shows adenocarcinoma
Biomarker testing: KRAS G12C mutation, PD-L1 TPS 0%
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72-year-old man who quit smoking 35 years ago (30 pack-years) was found to have a 3.4-cm RML
mass on a coronary calcium scan
PET CT: 3.4-cm x 3.4-cm RML mass, right hilar and subcarinal adenopathy, and L1, 12th rib, and left
scapular metastases
MRI brain: negative for metastasis
Comorbidities: HTN, gout, hyperlipidemia
ECOG 0 at diagnosis
He is now noting mild left upper back pain
Pathology: EBUS shows adenocarcinoma
Biomarker testing: KRAS G12C mutation, PD-L1 TPS 0%
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The Landscape of Lung Cancer’?
Not
‘otherwise
Specitied
Es
PD-L1 expression
‘Tumor mutational burden
Histology
1. os: targetedone comiewidiagnoss-staging-and-testing for-nonsquamous-nele 2. Addeo A etal, Cancer Treat Rev. 2021;96:102179, PeerView.com
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Not
‘otherwise
Specitied
Es
PD-L1 expression
‘Tumor mutational burden
Histology
1. os: targetedone comiewidiagnoss-staging-and-testing for-nonsquamous-nele 2. Addeo A etal, Cancer Treat Rev. 2021;96:102179, PeerView.com
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The Advent of Immunotherapy
The New ork Times
BUSINESS DAY
F.D.A. Allows First Use of a Novel Cancer Drug
By ANDREW POLLACK. SEPT. 4,204
‘The Food and Drug Administration on Thursday approved the first of an
eagerly awaited new class of cancer drugs that unleashes the body's
immune system to fight tumors.
‘The drug, which Merck will sell under the name — %* was approved
for patients with advanced melanoma who have exhausted other therapies.
Cancer researchers have been almost giddy in the last couple of years about
the potential of drugs like % ‚which seem to solve a century-old
mystery of how cancerous cells manage to evade the body's immune
system.
+ Pembrolizumab %
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The New ork Times
BUSINESS DAY
F.D.A. Allows First Use of a Novel Cancer Drug
By ANDREW POLLACK. SEPT. 4,204
‘The Food and Drug Administration on Thursday approved the first of an
eagerly awaited new class of cancer drugs that unleashes the body's
immune system to fight tumors.
‘The drug, which Merck will sell under the name — %* was approved
for patients with advanced melanoma who have exhausted other therapies.
Cancer researchers have been almost giddy in the last couple of years about
the potential of drugs like % ‚which seem to solve a century-old
mystery of how cancerous cells manage to evade the body's immune
system.
+ Pembrolizumab %
PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
The Advent of Immunotherapy
PeerView.com/XRX827
The New York Times
F.D.A. Allows First Use of a Novel Cancer Drug
By ANDREW POLLACK. SEPT. 4,204
‘The Food and Drug Administration on Thursday approved the first of an
eagerly awaited new class of cancer drugs that unleashes the body's
immune system to fight tumors.
‘The drug, which Merck will sell under the name # was approved
for patients with advanced melanoma who have exhausted other therapies.
Cancer researchers have been ainosfganfn the last couple of years about
the potential of drugslike # _ , which seem to solve a century-old
mystery of how cancerous cells manage to evade the body's immune
system
+ Pembrolizumab 5
PeerView.com
Copyright © 2000-2024, Peerview
PeerView.com/XRX827
The New York Times
F.D.A. Allows First Use of a Novel Cancer Drug
By ANDREW POLLACK. SEPT. 4,204
‘The Food and Drug Administration on Thursday approved the first of an
eagerly awaited new class of cancer drugs that unleashes the body's
immune system to fight tumors.
‘The drug, which Merck will sell under the name # was approved
for patients with advanced melanoma who have exhausted other therapies.
Cancer researchers have been ainosfganfn the last couple of years about
the potential of drugslike # _ , which seem to solve a century-old
mystery of how cancerous cells manage to evade the body's immune
system
+ Pembrolizumab 5
PeerView.com
Copyright © 2000-2024, Peerview
Immunotherapy: How Does It Work?
Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
Tumor Microenvironment
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Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
Tumor Microenvironment
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Immunotherapy: How Does It Work?
Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
PD-1 pathway inhibits signaling
downstream of TCR
presented by tumor cell 3 E
+ Negative regulatory receptor
PD-1 expressed and PD-L1
reactively expressed
+ PD-L1 binds to PD-1
sw 7 =
Tumor escape
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Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
PD-1 pathway inhibits signaling
downstream of TCR
presented by tumor cell 3 E
+ Negative regulatory receptor
PD-1 expressed and PD-L1
reactively expressed
+ PD-L1 binds to PD-1
sw 7 =
Tumor escape
PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Immunotherapy: How Does It Work?
Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
PD-1 pathway inhibits signaling
downstream of TCR
+ TCR triggered by antigen
presented by tumor cell
+ Negative regulatory receptor
Anti-PD-1 or anti-PD-L1
monocional antibodies
block the interaction
PD-1 expressed and PD-L1 and negative regulation
reactively expressed
+ PD-L1 binds to PD-1
A Eimnbinet
PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
PD-1 pathway inhibits signaling
downstream of TCR
+ TCR triggered by antigen
presented by tumor cell
+ Negative regulatory receptor
Anti-PD-1 or anti-PD-L1
monocional antibodies
block the interaction
PD-1 expressed and PD-L1 and negative regulation
reactively expressed
+ PD-L1 binds to PD-1
A Eimnbinet
PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Immunotherapy: How Does It Work?
Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
PD-1 pathway inhibits signaling
downstream of TCR
+ TCR triggered by antigen
presented by tumor cell
+ Negative regulatory receptor
Anti-PD-1 or anti-PD-L1
monocional antibodies
block the interaction
PD-1 expressed and PD-L1 and negative regulation
reactively expressed
+ PD-L1 binds to PD-1
T cell activated
Tumor esse | Eimsstonet
Anti-PD-1
therapies used
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PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
PD-1 pathway inhibits signaling
downstream of TCR
+ TCR triggered by antigen
presented by tumor cell
+ Negative regulatory receptor
Anti-PD-1 or anti-PD-L1
monocional antibodies
block the interaction
PD-1 expressed and PD-L1 and negative regulation
reactively expressed
+ PD-L1 binds to PD-1
T cell activated
Tumor esse | Eimsstonet
Anti-PD-1
therapies used
PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Immunotherapy: How Does It Work?
Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
PD-1 pathway inhibits signaling
downstream of TCR
+ TCR triggered by antigen
presented by tumor cell
+ Negative regulatory receptor
PD-1 expressed and PD-L1
reactively expressed
+ PD-L1 binds to PD-1
Anti-PD-1 or anti-PD-L1
monoclonal antibodies
block the interaction
and negative regulation
T cell activated
ances
Anti-PD-1
therapies used
Anti-PD-L1
therapies used
in NSCLC
Atezolizumab
Durvalumab
PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
Immune Checkpoint Inhibitors Block T-Cell Inhibitory Signals
PD-1/PD-L1 Checkpoint Inhibition
PD-1 pathway inhibits signaling
downstream of TCR
+ TCR triggered by antigen
presented by tumor cell
+ Negative regulatory receptor
PD-1 expressed and PD-L1
reactively expressed
+ PD-L1 binds to PD-1
Anti-PD-1 or anti-PD-L1
monoclonal antibodies
block the interaction
and negative regulation
T cell activated
ances
Anti-PD-1
therapies used
Anti-PD-L1
therapies used
in NSCLC
Atezolizumab
Durvalumab
PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
Approvals for First-Line Immunotherapy
in Advanced NSCLC12
Immunotherapy alone can be active in tumors with high PD-L1 expression
2016 2017 019 2020 2021 2022
E
5 Pembrolizumab Pembrolizumab Cae Cemiplimab
$ (PD-L1 250%, (PD-L1 21%, ee (PD-L1 250%,
2 no EGFR/ALK) no EGFR/ALK) ESFRALIO no EGFR/ALK)
E KEYNOTE-024 KEYNOTE-042 IMpower110 EMPOWEI ine
ÉE
1. Adapted trom Zhou Feta, Col Mol Immunol, 2021:18:270:203.2. Gogishvil M tal, Nat Med. 2022:28:2374-2380, PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
in Advanced NSCLC12
Immunotherapy alone can be active in tumors with high PD-L1 expression
2016 2017 019 2020 2021 2022
E
5 Pembrolizumab Pembrolizumab Cae Cemiplimab
$ (PD-L1 250%, (PD-L1 21%, ee (PD-L1 250%,
2 no EGFR/ALK) no EGFR/ALK) ESFRALIO no EGFR/ALK)
E KEYNOTE-024 KEYNOTE-042 IMpower110 EMPOWEI ine
ÉE
1. Adapted trom Zhou Feta, Col Mol Immunol, 2021:18:270:203.2. Gogishvil M tal, Nat Med. 2022:28:2374-2380, PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Approvals for First-Line Immunotherapy
in Advanced NSCLC12
Immunotherapy alone can be active in tumors with high PD-L1 expression
But what about PD-L1 <50%? Or <1%?
2016 2017 201 019 2020 2021 2022
5
5 Pembrolizumab Pembrolizumab Cate Cemiplimab
$ (PD-L1 250%, (PD-L1 21%, a (PD-L1 250%,
2 no EGFR/ALK) no EGFR/ALK) ESFRALIO no EGFR/ALK)
{Adapted rom Zhou Fetal. Co Mol Immunol 2021:19:270-259. 2. GogihviiM etal, Nat Med. 202228:2974-236. PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
in Advanced NSCLC12
Immunotherapy alone can be active in tumors with high PD-L1 expression
But what about PD-L1 <50%? Or <1%?
2016 2017 201 019 2020 2021 2022
5
5 Pembrolizumab Pembrolizumab Cate Cemiplimab
$ (PD-L1 250%, (PD-L1 21%, a (PD-L1 250%,
2 no EGFR/ALK) no EGFR/ALK) ESFRALIO no EGFR/ALK)
{Adapted rom Zhou Fetal. Co Mol Immunol 2021:19:270-259. 2. GogihviiM etal, Nat Med. 202228:2974-236. PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Approvals for First-Line Immunotherapy
in Advanced NSCLC12
Immunotherapy alone can be active in tumors with high PD-L1 expression
2020 2021 2022
A S Atezolizumab Nivolumab + .
Pembrolizumab Pembrolizumab (PD-L1 250% or Tollmumab Cemiplimab
(PD-L1 250%, (PD-L1 21%, Rats (PD-L1 21%, (PD-L1 250%,
no EGFR/ALK) no EGFR/ALK) EGFR/ALK) no EGFR/ALK) no EGFR/ALK)
KEYNOTE-024 KEYNOTE-042 IMpower110 CheckMate -227 | EMPOWER-Lung-1
PeerView.com
Immunotherapy
1. Adapted trom Zhou Feta Col Mol Immunol. 2021:18:279-293. 2. Gogishvil M tal, Nat Med. 2022:28:2374-2380,
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
in Advanced NSCLC12
Immunotherapy alone can be active in tumors with high PD-L1 expression
2020 2021 2022
A S Atezolizumab Nivolumab + .
Pembrolizumab Pembrolizumab (PD-L1 250% or Tollmumab Cemiplimab
(PD-L1 250%, (PD-L1 21%, Rats (PD-L1 21%, (PD-L1 250%,
no EGFR/ALK) no EGFR/ALK) EGFR/ALK) no EGFR/ALK) no EGFR/ALK)
KEYNOTE-024 KEYNOTE-042 IMpower110 CheckMate -227 | EMPOWER-Lung-1
PeerView.com
Immunotherapy
1. Adapted trom Zhou Feta Col Mol Immunol. 2021:18:279-293. 2. Gogishvil M tal, Nat Med. 2022:28:2374-2380,
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Approvals for First-Line Immunotherapy
in Advanced NSCLC12
Immunotherapy alone can be active in tumors with high PD-L1 expression
Immunotherapy combinations might be more active than single agents
2016 2017 201 019 2020 2021 2022
E
5 Pembrolizumab Pembrolizumab Caney . ee Cemiplimab
$ (PD-L1 250%, (PD-L1 21%, oa (shee (PD-L1 250%,
2 no EGFR/ALK) no EGFR/ALK) ESFRALIO no EGFRIAL) no EGFR/ALK)
1 Adapted from Zhou F et al Cel Mol Immunol. 2021:18:278-283. 2. Gogisvi Metal. Nat Med. 2022.28:2374-230. PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
in Advanced NSCLC12
Immunotherapy alone can be active in tumors with high PD-L1 expression
Immunotherapy combinations might be more active than single agents
2016 2017 201 019 2020 2021 2022
E
5 Pembrolizumab Pembrolizumab Caney . ee Cemiplimab
$ (PD-L1 250%, (PD-L1 21%, oa (shee (PD-L1 250%,
2 no EGFR/ALK) no EGFR/ALK) ESFRALIO no EGFRIAL) no EGFR/ALK)
1 Adapted from Zhou F et al Cel Mol Immunol. 2021:18:278-283. 2. Gogisvi Metal. Nat Med. 2022.28:2374-230. PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Approvals for First-Line Immunotherapy
in Advanced NSCLC'
Immunotherapy alone can be active in tumors with high PD-L1 expression
Immunotherapy combinations might be more active than single agents
But do we have other combination options?
2016 2017 201 2019 2020 2021 2022
E
5 Pembrolizumab Pembrolizumab Cae 4 ane Cemiplimab
$ (PD-L1 250%, (PD-L1 21%, as OR. (PD-L1 250%,
2 no EGFR/ALK) no EGFR/ALK) an en no EGFR/ALK)
Y Adapted rom Zhou F et al Col Mol Immunol. 2021:18:278-283. 2. Gogishvil Metal. Nat Med, 2022.28:2374-230. PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
in Advanced NSCLC'
Immunotherapy alone can be active in tumors with high PD-L1 expression
Immunotherapy combinations might be more active than single agents
But do we have other combination options?
2016 2017 201 2019 2020 2021 2022
E
5 Pembrolizumab Pembrolizumab Cae 4 ane Cemiplimab
$ (PD-L1 250%, (PD-L1 21%, as OR. (PD-L1 250%,
2 no EGFR/ALK) no EGFR/ALK) an en no EGFR/ALK)
Y Adapted rom Zhou F et al Col Mol Immunol. 2021:18:278-283. 2. Gogishvil Metal. Nat Med, 2022.28:2374-230. PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
Immunotherapy: How Does It Work?
Rationale for Chemotherapy Combinations With Immunotherapy‘
Chemotherapy: MOA Priming
Chemotherapy
1.Chen DS, Melman I. Immunity. 2013:39:1-10,
PeerView.com/XRX827
Immune Checkpoint MOA
APC priming and D Cytotoxic T cots
activation of Tells
Cytotoxic T cats
Infirate tumors
ome en ©
2 n
by dena cals lower"
and APCS recognition
cancer cols
Cancer call death Immune c
and release O) iar cancer coto
of cancer col
‘antigens
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Copyright © 2000-2024, Peerview
Rationale for Chemotherapy Combinations With Immunotherapy‘
Chemotherapy: MOA Priming
Chemotherapy
1.Chen DS, Melman I. Immunity. 2013:39:1-10,
PeerView.com/XRX827
Immune Checkpoint MOA
APC priming and D Cytotoxic T cots
activation of Tells
Cytotoxic T cats
Infirate tumors
ome en ©
2 n
by dena cals lower"
and APCS recognition
cancer cols
Cancer call death Immune c
and release O) iar cancer coto
of cancer col
‘antigens
PeerView.com
Copyright © 2000-2024, Peerview
Approvals for First-Line Immunotherapy
in Advanced NSCLC12
POWER-Lung
Cemiplimab + platinum chemo
(No EGFR/ALK/ROS1)
§ © Pembrolizumab ESE + paclitaxel Atezolizumab
€s + pemetrexed Pembrolizumab + carboplatin + nab-paclitaxel Nivolumab Durvalumab
© 5 +Platinumchemo + nab-pacltaxel ie bevacizumab + carboplatin + ipilimumab + tremelimumab
E (nonsquamous, + carboplatin nonsquamouS, (nonsquamous, + chemo x 2 + chemo x 4
2 8 5 EOFRIALK) (squamous) No EGFR/ALK) no EGFR/ALK) (no EGFR/ALK) | (no EGFR/ALK)
— | |
2020
2021 2022
>
2
2 9
5 Pembrolizumab Pembrolizumab met Aeon Cemiplimab
4 (PD-L1 250%, (PD-L1 21%, ( ine pa He (PD-L1 250%,
E no EGFR/ALK) no EGFR/ALK) Knie, MA EGPRALK) "O EGFR/ALK)
Y Adapted from Zhou F et al Col Mol Immunol. 2021:18:278-283. 2. Gogishvll Metal. Nat Med. 2022.28:2374-230. PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
in Advanced NSCLC12
POWER-Lung
Cemiplimab + platinum chemo
(No EGFR/ALK/ROS1)
§ © Pembrolizumab ESE + paclitaxel Atezolizumab
€s + pemetrexed Pembrolizumab + carboplatin + nab-paclitaxel Nivolumab Durvalumab
© 5 +Platinumchemo + nab-pacltaxel ie bevacizumab + carboplatin + ipilimumab + tremelimumab
E (nonsquamous, + carboplatin nonsquamouS, (nonsquamous, + chemo x 2 + chemo x 4
2 8 5 EOFRIALK) (squamous) No EGFR/ALK) no EGFR/ALK) (no EGFR/ALK) | (no EGFR/ALK)
— | |
2020
2021 2022
>
2
2 9
5 Pembrolizumab Pembrolizumab met Aeon Cemiplimab
4 (PD-L1 250%, (PD-L1 21%, ( ine pa He (PD-L1 250%,
E no EGFR/ALK) no EGFR/ALK) Knie, MA EGPRALK) "O EGFR/ALK)
Y Adapted from Zhou F et al Col Mol Immunol. 2021:18:278-283. 2. Gogishvll Metal. Nat Med. 2022.28:2374-230. PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
Let’s Summarize: Treatment Algorithm for Metastatic NSCLC
With No Actionable Genomic Alterations!
Chemotherapy + Immune Checkpoint Inhibitor Moca, ee
Pembrolizumab Therapy
+ Carboplatin/pemetrexed/pembrolizumab (NSQ) AtedEemab Nivofpi
Cemiplimab
+ Carboplatin/paclitaxel/atezolizumab/bevacizumab (NSQ)
Advanced
NSCLC Carboplatin/nab-paclitaxel/atezolizumab (NSQ) ici ICI Combo
Monotherapy Therapy
First Line Carboplatin/taxane/pembrolizumab (SQ) Pembrolizumab* Nivofipi
No Driver
Nivolumabjipilimumab/chemo (SQ and NSQ)
Durvalumab/tremelimumab/chemo (SQ and NSQ)
Cemiplimab/chemo (SQ and NSQ)
* Pembrolzumab alone isnot ley superior o chemo in PO-L1 1%-49%—combmatons favored. m
1. Adapted rom Doroshow D. NACL 2020 PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
With No Actionable Genomic Alterations!
Chemotherapy + Immune Checkpoint Inhibitor Moca, ee
Pembrolizumab Therapy
+ Carboplatin/pemetrexed/pembrolizumab (NSQ) AtedEemab Nivofpi
Cemiplimab
+ Carboplatin/paclitaxel/atezolizumab/bevacizumab (NSQ)
Advanced
NSCLC Carboplatin/nab-paclitaxel/atezolizumab (NSQ) ici ICI Combo
Monotherapy Therapy
First Line Carboplatin/taxane/pembrolizumab (SQ) Pembrolizumab* Nivofipi
No Driver
Nivolumabjipilimumab/chemo (SQ and NSQ)
Durvalumab/tremelimumab/chemo (SQ and NSQ)
Cemiplimab/chemo (SQ and NSQ)
* Pembrolzumab alone isnot ley superior o chemo in PO-L1 1%-49%—combmatons favored. m
1. Adapted rom Doroshow D. NACL 2020 PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, Peerview
Let’s Summarize: Treatment Algorithm for Metastatic NSCLC
With No Actionable Genomic Alterations!
No head-to-head data!
How to select treatment?
Disease burden
Symptom severity
Performance status
Histology
History of autoimmunity
Comorbidities
Patient goals and preferences
* Pembrolzumab alone is not clearly superior o chemo in PO-L1 1%-49%—combinations favored
1 Adapted from
PeerView.com/XRX827
Doroshow D. NALCC 2020.
>
PeerView.com
Copyright © 2000-2024, PeerView
With No Actionable Genomic Alterations!
No head-to-head data!
How to select treatment?
Disease burden
Symptom severity
Performance status
Histology
History of autoimmunity
Comorbidities
Patient goals and preferences
* Pembrolzumab alone is not clearly superior o chemo in PO-L1 1%-49%—combinations favored
1 Adapted from
PeerView.com/XRX827
Doroshow D. NALCC 2020.
>
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Returning to Our Case
72-year-old man who quit smoking 35 years ago (30 pack-years) was found to have a 3.4-cm RML
mass on a coronary calcium scan
PET CT: 3.4-cm x 3.4-cm RML mass, right hilar and subcarinal adenopathy, and L1, 12th rib, and left
scapular metastases
MRI brain: negative for metastasis
Comorbidities: HTN, gout, hyperlipidemia Teaching points
ECOG 0 at diagnosis + No first-line targeted therapy
He is now noting mild left upper back pain for KRAS-mutated NSCLC
Pathology: EBUS shows adenocarcinoma + No single-agent ICI for PD-L1 0%
Molecular: KRAS G12C mutation, PD-L1 TPS 0% + Multiple combos are reasonable
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72-year-old man who quit smoking 35 years ago (30 pack-years) was found to have a 3.4-cm RML
mass on a coronary calcium scan
PET CT: 3.4-cm x 3.4-cm RML mass, right hilar and subcarinal adenopathy, and L1, 12th rib, and left
scapular metastases
MRI brain: negative for metastasis
Comorbidities: HTN, gout, hyperlipidemia Teaching points
ECOG 0 at diagnosis + No first-line targeted therapy
He is now noting mild left upper back pain for KRAS-mutated NSCLC
Pathology: EBUS shows adenocarcinoma + No single-agent ICI for PD-L1 0%
Molecular: KRAS G12C mutation, PD-L1 TPS 0% + Multiple combos are reasonable
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What About Immunotherapy
in Earlier Stages of NSCLC?
in Earlier Stages of NSCLC?
Unresectable Stage III NSCLC’
PACIFIC: Durvalumab vs Placebo x 1 Year After Chemoradiation
os
Evrard 05 mo 05% 00
— a soar) =
Pac sr usa 201021351) pes
O]
10 um ‘Stated om Dar ans 008 8% C1. 088087) 1 ‘States om per sa 052 9% C042 068)
qe E a
ga o aro ar
Be s H TN man Ba zon
sz sn
nam ee Bars,
1. Spige OR etal Cin Oncol 202240:1301.1311 PeerView.com
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PACIFIC: Durvalumab vs Placebo x 1 Year After Chemoradiation
os
Evrard 05 mo 05% 00
— a soar) =
Pac sr usa 201021351) pes
O]
10 um ‘Stated om Dar ans 008 8% C1. 088087) 1 ‘States om per sa 052 9% C042 068)
qe E a
ga o aro ar
Be s H TN man Ba zon
sz sn
nam ee Bars,
1. Spige OR etal Cin Oncol 202240:1301.1311 PeerView.com
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Resectable NSCLC: Overview
of Key Phase 3 Immunotherapy Trials
of Key Phase 3 Immunotherapy Trials
Resectable NSCLC: Overview of Key Phase 3 Neoadjuvant
and Adjuvant Immunotherapy Trials
Neoadjuvant Immunotherapy (Approved) SURGERY
CheckMate-816 _Nivolumab + chemo x 3 cycles ERAN
SURGERY Adjuvant Immunotherapy (Approved)
IMpower010 ‚Chemo > atezolizumab ~1 y (PD-L1 21%)
KEYNOTE-091 Chemo (optional) > pembrolizumab ~1 year
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and Adjuvant Immunotherapy Trials
Neoadjuvant Immunotherapy (Approved) SURGERY
CheckMate-816 _Nivolumab + chemo x 3 cycles ERAN
SURGERY Adjuvant Immunotherapy (Approved)
IMpower010 ‚Chemo > atezolizumab ~1 y (PD-L1 21%)
KEYNOTE-091 Chemo (optional) > pembrolizumab ~1 year
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CheckMate -816: pCR Rate (Primary Endpoint)’
pCR Rate With Neoadjuvant Nivo + Chemo vs Chemo
Primary endpoint
ITT (ypTONO)
40 OR = 13.94 (99% CI, 3.49-55.75)
P<.0001
Difference
=” 21.6%
cy
5
& 2
7
$
2
Nivo + Chemo Chemo
43/179 41179
1. Forde PM et a AACR 2021. Abstract TOO PeerView.com
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pCR Rate With Neoadjuvant Nivo + Chemo vs Chemo
Primary endpoint
ITT (ypTONO)
40 OR = 13.94 (99% CI, 3.49-55.75)
P<.0001
Difference
=” 21.6%
cy
5
& 2
7
$
2
Nivo + Chemo Chemo
43/179 41179
1. Forde PM et a AACR 2021. Abstract TOO PeerView.com
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CheckMate -816: EFS12
Primary Endpoint: EFS* With Neoadjuvant Nivo + Chemo vs Chemo
76%
Minimum Follow-Up: 21 mo; Median Follow-Up: 29.5 mo
Nivo + chemo
Chemo
80
E 60
a
e
Wi 40
179) 179)
20 + Median EFS: mo 316 208
HR (97.38% ci 0.63 (043.091)
— — — r A
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42
Time, mo
No. at Risk
Nivo +chemo 179 151 136 124 118 107 102 87 74 41 34
Chemo 179 144 126 109 94 83 75 61 52 26 24
13 6 3 0
13 1 4 0
"Per BICR. EFS defined as the time om randomizaton to any progression of disease precluding surgery. progression, or ecurence of disease añer super, progression fr patients wiheut super.
‘death due to any cate; patients wth subsequent therapy were censored at ie lat evaluable tumor assessment on or pri the date of ubsequent therapy, 95% Cl, 302.NR (rive + chemo)
and 140287 (chemo) © 95% Ci, 045-087. * The sigiicance Boundary at is intr analysts was 0282.
Y Girard N et al AACR 2022, Abstract CTO12 2, Forde PM et ai. N Eng J Med. 2022:26:386-1979-1986,
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Primary Endpoint: EFS* With Neoadjuvant Nivo + Chemo vs Chemo
76%
Minimum Follow-Up: 21 mo; Median Follow-Up: 29.5 mo
Nivo + chemo
Chemo
80
E 60
a
e
Wi 40
179) 179)
20 + Median EFS: mo 316 208
HR (97.38% ci 0.63 (043.091)
— — — r A
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42
Time, mo
No. at Risk
Nivo +chemo 179 151 136 124 118 107 102 87 74 41 34
Chemo 179 144 126 109 94 83 75 61 52 26 24
13 6 3 0
13 1 4 0
"Per BICR. EFS defined as the time om randomizaton to any progression of disease precluding surgery. progression, or ecurence of disease añer super, progression fr patients wiheut super.
‘death due to any cate; patients wth subsequent therapy were censored at ie lat evaluable tumor assessment on or pri the date of ubsequent therapy, 95% Cl, 302.NR (rive + chemo)
and 140287 (chemo) © 95% Ci, 045-087. * The sigiicance Boundary at is intr analysts was 0282.
Y Girard N et al AACR 2022, Abstract CTO12 2, Forde PM et ai. N Eng J Med. 2022:26:386-1979-1986,
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CheckMate -816: EFS12
Primary Endpoii
Minimum Follow-Up: 21 mo; Median Follow-Up: 29.5 mo
EFS*> With Neoadjuvant Nivo + Chemo vs Chemo
100
80
= 60
2 Nivo + chemo
w 40 45% Chemo
20 3-Year Update?
Be SUECIA + Landmark EFS rate 57% with nivo + chemo vs 43%
0 With chemo alone (HR = 0.68; 95% CI, 0.49-0.93)
+ OS immature, but 78% alive at 3 years vs 64% with
chemo alone (HR = 0.62; 99.34% Cl 0.36-1.05)
No. at Risk
Nivo+chemo 179 151 136 124 118 107 102 87 m 41 M 13 6 3 0
‘Chemo 179 144 126 109 94 83 75 61 52 26 24 13 11 4 0
Per ICR. > EFS defined ase te rom randomization 1 any progression of dase precung suger. progression or recurenc ol disease aer surgery Progression tr supe.
a cau du any cave pants ui suene were cond al sl eve Lmor seme en opr ow date of subsequent apy, CL 30 LÍO chee)
nd 140267 (emo) 68% C1 045087. Me Boundary as nam ana was 0282
Vara Wet ANCR 2022. Abstract C1012 2 For PM et a N Eng Y Med, 202236300 1973-1088. 2, Fore PM et. ELEC 202, Abarat 40. PeerView.com
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Primary Endpoii
Minimum Follow-Up: 21 mo; Median Follow-Up: 29.5 mo
EFS*> With Neoadjuvant Nivo + Chemo vs Chemo
100
80
= 60
2 Nivo + chemo
w 40 45% Chemo
20 3-Year Update?
Be SUECIA + Landmark EFS rate 57% with nivo + chemo vs 43%
0 With chemo alone (HR = 0.68; 95% CI, 0.49-0.93)
+ OS immature, but 78% alive at 3 years vs 64% with
chemo alone (HR = 0.62; 99.34% Cl 0.36-1.05)
No. at Risk
Nivo+chemo 179 151 136 124 118 107 102 87 m 41 M 13 6 3 0
‘Chemo 179 144 126 109 94 83 75 61 52 26 24 13 11 4 0
Per ICR. > EFS defined ase te rom randomization 1 any progression of dase precung suger. progression or recurenc ol disease aer surgery Progression tr supe.
a cau du any cave pants ui suene were cond al sl eve Lmor seme en opr ow date of subsequent apy, CL 30 LÍO chee)
nd 140267 (emo) 68% C1 045087. Me Boundary as nam ana was 0282
Vara Wet ANCR 2022. Abstract C1012 2 For PM et a N Eng Y Med, 202236300 1973-1088. 2, Fore PM et. ELEC 202, Abarat 40. PeerView.com
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Resectable NSCLC: Overview of Key Phase 3 Perioperative
(Neoadjuvant > Adjuvant) Immunotherapy Trials!
Neoadjuvant
(Chemo-10
vs Chemo)
EGFR/
ALK
Adjuvant
(10 1 y vs Placebo)
Stage
Primary DFS/EFS
Endpoint
HR
DFSIEFS
Rate, %
N)
os
Rate, %
w
Durvalumab
AEGEAN
+ chemo
(AACR 2023) CEE)
KEYNOTE-671 — Pembrolizumab
(ASCO 2023) + chemo
(ESMO 2023) (4 cycles)
se
esi” Toes
(4 cycles)
—
PeerView.com/XRX827
802 Excluded
786 Included
Excluded
481 known)
Durvalumab
Pembrolizumab
Nivolumab
AB,
pane,
(eth
ed)
tag
(th
ed)
PCR
EFS
EFS
os
EFS
068
059
0.58
63(2)
62(2)
70(1.5)
NR NR
79 (2)
716) 072
67 (4)
NR NR
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(Neoadjuvant > Adjuvant) Immunotherapy Trials!
Neoadjuvant
(Chemo-10
vs Chemo)
EGFR/
ALK
Adjuvant
(10 1 y vs Placebo)
Stage
Primary DFS/EFS
Endpoint
HR
DFSIEFS
Rate, %
N)
os
Rate, %
w
Durvalumab
AEGEAN
+ chemo
(AACR 2023) CEE)
KEYNOTE-671 — Pembrolizumab
(ASCO 2023) + chemo
(ESMO 2023) (4 cycles)
se
esi” Toes
(4 cycles)
—
PeerView.com/XRX827
802 Excluded
786 Included
Excluded
481 known)
Durvalumab
Pembrolizumab
Nivolumab
AB,
pane,
(eth
ed)
tag
(th
ed)
PCR
EFS
EFS
os
EFS
068
059
0.58
63(2)
62(2)
70(1.5)
NR NR
79 (2)
716) 072
67 (4)
NR NR
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Summary: Current Role of Immunotherapy in NSCLC
Metastatic Disease
PD-(L)1 inhibitor alone, especially in patients with high PD-L1
PD-L1 + CTLA-4 inhibition
Chemo combinations with PD-L1 + CTLA-4 inhibition
Early Stage
Resectable
Neoadjuvant therapy: nivolumab + chemo.
Perioperative therapy: pembrolizumab + chemo > surgery > pembrolizumab
Adjuvant therapy: atezolizumab (PD-L1+) or pembrolizumab
Unresectable
Durvalumab after chemoradiation
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Metastatic Disease
PD-(L)1 inhibitor alone, especially in patients with high PD-L1
PD-L1 + CTLA-4 inhibition
Chemo combinations with PD-L1 + CTLA-4 inhibition
Early Stage
Resectable
Neoadjuvant therapy: nivolumab + chemo.
Perioperative therapy: pembrolizumab + chemo > surgery > pembrolizumab
Adjuvant therapy: atezolizumab (PD-L1+) or pembrolizumab
Unresectable
Durvalumab after chemoradiation
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MasterClass 2
Maximizing the Benefits of Immunotherapies
in NSCLC: How Nurses and the Care Team
Recognize and Mitigate irAEs
Marianne Davies, DNP, ACNP, AOCNP, FAAN
Program Manager Care Signature, Oncology
Oncology Nurse Practitioner
Yale Comprehensive Cancer Center & Smilow Cancer Center
Associate Professor
Yale School of Nursing
New Haven, Connecticut
Copyright © 2000-2024, PeerView
Maximizing the Benefits of Immunotherapies
in NSCLC: How Nurses and the Care Team
Recognize and Mitigate irAEs
Marianne Davies, DNP, ACNP, AOCNP, FAAN
Program Manager Care Signature, Oncology
Oncology Nurse Practitioner
Yale Comprehensive Cancer Center & Smilow Cancer Center
Associate Professor
Yale School of Nursing
New Haven, Connecticut
Copyright © 2000-2024, PeerView
irAE Management: Key Pillars
Monitoring
Medication
Reconciliation
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Monitoring
Medication
Reconciliation
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irAEs Can Affect Any Organ System!
Neurologie
+ Meninglisiencephalts
+ GullainBarré
+ Myelopalnyineuropatny
+ Myasthenia
Eye
+" Uvetisscents
Conjunctivitis/blepharitis
+ Reine
+ Sicca syndrome
Cardiovascular
+ Myocarditis
- Pericartis
+ Vascas
+ Pancreatitis 1% to <10%
<1%
+ Hemophilia
1.Haanen JB eta. Ann Oncol. 2017:28iv19-v142. 2. Postow MA et al. N Engl J Med, 2018:378:158-168 =
3. Gordon R etal. Cin J Oncol Murs. 2017:21(supp 2)45-52. 4. Darnell EP eta. Curr Oncal Rep. 2020.22: PeerView.com
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Neurologie
+ Meninglisiencephalts
+ GullainBarré
+ Myelopalnyineuropatny
+ Myasthenia
Eye
+" Uvetisscents
Conjunctivitis/blepharitis
+ Reine
+ Sicca syndrome
Cardiovascular
+ Myocarditis
- Pericartis
+ Vascas
+ Pancreatitis 1% to <10%
<1%
+ Hemophilia
1.Haanen JB eta. Ann Oncol. 2017:28iv19-v142. 2. Postow MA et al. N Engl J Med, 2018:378:158-168 =
3. Gordon R etal. Cin J Oncol Murs. 2017:21(supp 2)45-52. 4. Darnell EP eta. Curr Oncal Rep. 2020.22: PeerView.com
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Prevalence, Distribution, and Severity of irAEs13
Most Common irAEs of Special Interest
Grade
o 20 12 35
E = m plimumab
a 40 M & Ipilimumab + nivolumab
5 © Nivolumab.
8 15 = m Pembroizumab
5
a
2 30
3
2 10
5 2
2
8 5
5 10
3
3
É
Fi Pi Ra °
Diarrhea Fatigue Nausea Pruritus sh N sn Se ES we
y
SS a zn ow oo
1. Madden Gin J Oncol Nurs. 2017:21:30.2. Gordon R eta Clin J Oncol Nurs. 2017:21(suppl 2)45-52, 3. Puzanov et al.) Immunother Cancer. 2017:595. PeerView.com
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Most Common irAEs of Special Interest
Grade
o 20 12 35
E = m plimumab
a 40 M & Ipilimumab + nivolumab
5 © Nivolumab.
8 15 = m Pembroizumab
5
a
2 30
3
2 10
5 2
2
8 5
5 10
3
3
É
Fi Pi Ra °
Diarrhea Fatigue Nausea Pruritus sh N sn Se ES we
y
SS a zn ow oo
1. Madden Gin J Oncol Nurs. 2017:21:30.2. Gordon R eta Clin J Oncol Nurs. 2017:21(suppl 2)45-52, 3. Puzanov et al.) Immunother Cancer. 2017:595. PeerView.com
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+ Chemotherapy fatalities: 1.4%
+ Immune checkpoint inhibitor fatality rates vary
—Anti-PD-1/L1: 0.25%-1.1%
— Anti-CTLA-4: 0.2%-1.1%
—Anti-PD-1/L1 + CTLA-4: 0.28%-1.23%
— ipiimumab
zo — Antro
= Combinaton
Ss
e ‘Median time to onset
Iplimumab: 40 days,
40 AN-PO-1: 40 days
E Combination: 14.5 days
lo
Time, d
No, at Risk
ee a 1520000 0
ato! M 1% § 2 2 2 0
Combination 6 0 0 0 0 0 0
* Includes 3,905 total cases.
Patients, %
3853838
Fatal irAEs*?
Mains
Mason
rosso ni cms
“SP SP IPOS P ?
Cases and Fatality Rates
EJ
Reported irAEs, n
4, Wang DY etal. JAMA Oncol, 2018:4:1721-1728, 2. Nihiima TF eta. Oncologist 2017;22:470-479,
PeerView.com/XRX827
y = E
Fatality Rate, %
PeerView.com
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+ Immune checkpoint inhibitor fatality rates vary
—Anti-PD-1/L1: 0.25%-1.1%
— Anti-CTLA-4: 0.2%-1.1%
—Anti-PD-1/L1 + CTLA-4: 0.28%-1.23%
— ipiimumab
zo — Antro
= Combinaton
Ss
e ‘Median time to onset
Iplimumab: 40 days,
40 AN-PO-1: 40 days
E Combination: 14.5 days
lo
Time, d
No, at Risk
ee a 1520000 0
ato! M 1% § 2 2 2 0
Combination 6 0 0 0 0 0 0
* Includes 3,905 total cases.
Patients, %
3853838
Fatal irAEs*?
Mains
Mason
rosso ni cms
“SP SP IPOS P ?
Cases and Fatality Rates
EJ
Reported irAEs, n
4, Wang DY etal. JAMA Oncol, 2018:4:1721-1728, 2. Nihiima TF eta. Oncologist 2017;22:470-479,
PeerView.com/XRX827
y = E
Fatality Rate, %
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Timing of irAE Occurrence’
+ Within weeks to months after initiation of therapy
+ May occur after ICIs are discontinued
+ Timing can be highly variable
+ Time course may be more variable in combination
treatment
Incidence
Pneumonitis
“Te, mo
1 2 3 4 5 6 eramos our
Months on Treatment re 7
1. Davies M, Dufild E.Immunotarges Ther. 2017:6:51-71 PeerView.com
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+ Within weeks to months after initiation of therapy
+ May occur after ICIs are discontinued
+ Timing can be highly variable
+ Time course may be more variable in combination
treatment
Incidence
Pneumonitis
“Te, mo
1 2 3 4 5 6 eramos our
Months on Treatment re 7
1. Davies M, Dufild E.Immunotarges Ther. 2017:6:51-71 PeerView.com
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irAEs Are Different From the AEs
Associated With Other Cancer Therapies
Chemotherapy Immunotherapy
Incidence of moderate/severe AEs Almost all patients Majority without
AE profile Well described
Affected systems/organs Few organs affected Any organ
Variable
Time course Well established Even after treatment ends
Predictable Relatively unpredictable
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Associated With Other Cancer Therapies
Chemotherapy Immunotherapy
Incidence of moderate/severe AEs Almost all patients Majority without
AE profile Well described
Affected systems/organs Few organs affected Any organ
Variable
Time course Well established Even after treatment ends
Predictable Relatively unpredictable
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Timeline and Potential Importance of Key Issues
Throughout the Course of Treatment With ICIs!
Patient/Toxicity-
Related Factors
, :
Tine nooo temen it 1 Y A
Tumor-Related
Factors
1.Johnsen DB et al. Net Rev Cin Oncol 2022:19:254-267 PeerView.com
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Throughout the Course of Treatment With ICIs!
Patient/Toxicity-
Related Factors
, :
Tine nooo temen it 1 Y A
Tumor-Related
Factors
1.Johnsen DB et al. Net Rev Cin Oncol 2022:19:254-267 PeerView.com
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Risk Factors Associated With irAEs!
- >60 years of age
+ ECOG PS >2
+ >50 pack-year smoking history
or current smoking
+ BMI >23 kg/m?
+ Sarcopenia and low muscle mass
+ High disease burden
+ Higher tumor mutational burden
+ Combination with chemotherapy
+ — Antibiotic use
+ Vitamin D deficiency
ICI dass and dosage
1.Suikerbuik KPM et al. Nat Cancer, 2024:5557-571 PeerView.com
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- >60 years of age
+ ECOG PS >2
+ >50 pack-year smoking history
or current smoking
+ BMI >23 kg/m?
+ Sarcopenia and low muscle mass
+ High disease burden
+ Higher tumor mutational burden
+ Combination with chemotherapy
+ — Antibiotic use
+ Vitamin D deficiency
ICI dass and dosage
1.Suikerbuik KPM et al. Nat Cancer, 2024:5557-571 PeerView.com
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General Recommendations for Treating irAEs!*
Managed in outpatient! Generally requires
community setting hospital admission
Strong immune suppr
reatment
Steroids (PO/IV): 1-2 mg/kg/d
Oral steroids —— intravenous steroids ——> prednisone or equivalent,
slowly taper over 4-6 weeks
For some AEs, treatment can be
restarted after resolution (eg, rash),
‘generally, ICI can be continued
with endocnnopathies once managed
Stop treatment —————__________»
‘Symptomatic and supportive therapy
= GG ©
Mild
Increasing intensity
of treatment required
Very saver Veran so
Increasing grade of irAE
1. Champiat 5. ESMO Patient Guide Series. htps vw esmo orgcontentéounlond/ 124 1307235280 1/1ESMO-Patient Guie-on-Immunotherapy-Side-Efects pal
2 hits:wnew.neen orgprotessionaliphysician_lspdtimmunctherapy pt. 3, Brahmer J etal. J Cin Once. 2018:36:1714-176. a
4. Puzanoy letal Y immunother Cancer 2017.55. PeerView.com
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Managed in outpatient! Generally requires
community setting hospital admission
Strong immune suppr
reatment
Steroids (PO/IV): 1-2 mg/kg/d
Oral steroids —— intravenous steroids ——> prednisone or equivalent,
slowly taper over 4-6 weeks
For some AEs, treatment can be
restarted after resolution (eg, rash),
‘generally, ICI can be continued
with endocnnopathies once managed
Stop treatment —————__________»
‘Symptomatic and supportive therapy
= GG ©
Mild
Increasing intensity
of treatment required
Very saver Veran so
Increasing grade of irAE
1. Champiat 5. ESMO Patient Guide Series. htps vw esmo orgcontentéounlond/ 124 1307235280 1/1ESMO-Patient Guie-on-Immunotherapy-Side-Efects pal
2 hits:wnew.neen orgprotessionaliphysician_lspdtimmunctherapy pt. 3, Brahmer J etal. J Cin Once. 2018:36:1714-176. a
4. Puzanoy letal Y immunother Cancer 2017.55. PeerView.com
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Guidelines for Steroid Therapy
Prevention and Anticipation
+ Gastritis
— High risk: NSAIDs, anticoagulation
— Give proton pump inhibitor or H2 blockers
+ Opportunistic infections
— Risk: >20 mg prednisone >4 weeks
— PJP: sulfamethoxazole/trimethoprim
— Fungal: fluconazole
+ Osteoporosis, osteopenia, fractures
— Risk: extended course of steroids
— Give calcium carbonate-vitamin D3 600 mg
(1,500 mg) 400 IU once daily
— Routine DEXA
+ Taper over 230 days
+ Long-term (>4-6 weeks) treatment is sometimes.
needed to prevent recurrence
+ Rapid taper not advised, as it may result in
recurrence/flare
+ Blood glucose
+ Potential for adrenal insufficiency
+ Muscle weakness
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Prevention and Anticipation
+ Gastritis
— High risk: NSAIDs, anticoagulation
— Give proton pump inhibitor or H2 blockers
+ Opportunistic infections
— Risk: >20 mg prednisone >4 weeks
— PJP: sulfamethoxazole/trimethoprim
— Fungal: fluconazole
+ Osteoporosis, osteopenia, fractures
— Risk: extended course of steroids
— Give calcium carbonate-vitamin D3 600 mg
(1,500 mg) 400 IU once daily
— Routine DEXA
+ Taper over 230 days
+ Long-term (>4-6 weeks) treatment is sometimes.
needed to prevent recurrence
+ Rapid taper not advised, as it may result in
recurrence/flare
+ Blood glucose
+ Potential for adrenal insufficiency
+ Muscle weakness
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SITC Consensus Definitions for irAEs
Natural History of irAEs
Patterns of irAEs
Response to irAE Treatment
Recurrent irAES
+ Occur in the same organ
+ Occur at least twice after ICI
discontinuation
Delayed/late-onset irAES
+ Occur >3 months after CI discontinuation]
QT,
Chronic irAEs
‘+ Persist beyond 3 months of ICI
discontinuation
‘Two subtypes
1. Chronic + active: ongoing
inflammation, requires ongoing
immunosuppression
2. Chronic + inactive: absence of
‘ongoing inflammation, not requiring
‘ongoing immunosuppression
N)
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Multisystem irAEs.
+ Occur concomitantly with another irAE
+ ¡rAES occurring in the same or different
organ system
or during treatment forthe first irAE
If occurring in the same system, they
affect different tissues
Csitc>
Socie for Immunscher of Cancer
Fr
Steroid-unresponsive irAEs
+ No clinical improvement after a standard
timeframe of guideline-based irAE-
directed steroid therapy
+ Steroid-refractory irAEs derived no
clinical benefit from steroids
Sterold-resistant irAES
+ Derived some clinical benefit without
resolution of the event
Steroid-dependent irAES
+ Some improvement with guideline-based
ItAE-directed steroid therapy; however, a
taper is not possible
+ irAES requiring ongoing steroids for 212
weeks are “chronically steroid
dependent”
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Natural History of irAEs
Patterns of irAEs
Response to irAE Treatment
Recurrent irAES
+ Occur in the same organ
+ Occur at least twice after ICI
discontinuation
Delayed/late-onset irAES
+ Occur >3 months after CI discontinuation]
QT,
Chronic irAEs
‘+ Persist beyond 3 months of ICI
discontinuation
‘Two subtypes
1. Chronic + active: ongoing
inflammation, requires ongoing
immunosuppression
2. Chronic + inactive: absence of
‘ongoing inflammation, not requiring
‘ongoing immunosuppression
N)
PeerView.com/XRX827
Multisystem irAEs.
+ Occur concomitantly with another irAE
+ ¡rAES occurring in the same or different
organ system
or during treatment forthe first irAE
If occurring in the same system, they
affect different tissues
Csitc>
Socie for Immunscher of Cancer
Fr
Steroid-unresponsive irAEs
+ No clinical improvement after a standard
timeframe of guideline-based irAE-
directed steroid therapy
+ Steroid-refractory irAEs derived no
clinical benefit from steroids
Sterold-resistant irAES
+ Derived some clinical benefit without
resolution of the event
Steroid-dependent irAES
+ Some improvement with guideline-based
ItAE-directed steroid therapy; however, a
taper is not possible
+ irAES requiring ongoing steroids for 212
weeks are “chronically steroid
dependent”
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® Dermatologic irAEs „u
Practice Ald
Rash, pruritus, psoriasis, eczema, lichenoid deposits, vitiligo, blistering, skin sloughing,
DRESS, bullous pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis
Report 2 Assess Support
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Practice Ald
Rash, pruritus, psoriasis, eczema, lichenoid deposits, vitiligo, blistering, skin sloughing,
DRESS, bullous pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis
Report 2 Assess Support
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© Gastrointestinal irAEs EA
Practice Ald
> cn (EE
Report Assess Support
es | ooo | eo
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Practice Ald
> cn (EE
Report Assess Support
es | ooo | eo
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© Endocrine irAEs EA
Practice Ald
Hypothyroidism, hypophysitis, adrenal insufficiency
+ ToH>tomUL
2 Lorean (1e mpg) Report Assess Support
TSH and toe Ta every 48 wee
> Bee
ae
I!
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Practice Ald
Hypothyroidism, hypophysitis, adrenal insufficiency
+ ToH>tomUL
2 Lorean (1e mpg) Report Assess Support
TSH and toe Ta every 48 wee
> Bee
ae
I!
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© Rheumatologic irAEs +
Download the
Practice Ald
Arthralgias, arthritis
Assess Support
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Download the
Practice Ald
Arthralgias, arthritis
Assess Support
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+
Download the
Practice Ald
Neurologic irAEs
Weakness, neuropathy, myasthenia gravis, Guillain-Barré, myelitis (CQ
Report Assess Support
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Download the
Practice Ald
Neurologic irAEs
Weakness, neuropathy, myasthenia gravis, Guillain-Barré, myelitis (CQ
Report Assess Support
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+
Download the
Practice Ald
ID)» <evated amyiaseripase, pancreatitis, hyperglycemia, diabetes ¿CO
@ Pancreatic irAEs
Report Assess Support
Hessen
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Download the
Practice Ald
ID)» <evated amyiaseripase, pancreatitis, hyperglycemia, diabetes ¿CO
@ Pancreatic irAEs
Report Assess Support
Hessen
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Assessment and Treatment Resources
Download the
Practice Ald
Management of
Immunotherapy-Related
Toxicities
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Download the
Practice Ald
Management of
Immunotherapy-Related
Toxicities
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@ Patient Education and Other Resources KA
From LUNGevity A
We are partnering with LUNGevity as part of this educational activity
Please download the online resource compendium!
IN LUNGEVITY +:
Transforming Lung Cancer e
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From LUNGevity A
We are partnering with LUNGevity as part of this educational activity
Please download the online resource compendium!
IN LUNGEVITY +:
Transforming Lung Cancer e
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Other Patient Education Resources
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ICI Survivors From NSCLC: Burden of Toxicity
and Its Management May Be Significant!
Retrospective analysis O 52% (50/114) 27% (31/114) of survivors
OOOO suis required ongoing management
experienced at of irAEs at 1 year
least one irAE
(SW
20 survivors
36% (114/317) of patients hea multiple
with advanced NSCLC irAES ; A
survived >1 year after initiation ue cn Ei
f anti-PD-1/PD-L1 therapy el ated
a immunosuppression
1. Hau ML et a. Oncologist, 2022:27:971-981 PeerView.com
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and Its Management May Be Significant!
Retrospective analysis O 52% (50/114) 27% (31/114) of survivors
OOOO suis required ongoing management
experienced at of irAEs at 1 year
least one irAE
(SW
20 survivors
36% (114/317) of patients hea multiple
with advanced NSCLC irAES ; A
survived >1 year after initiation ue cn Ei
f anti-PD-1/PD-L1 therapy el ated
a immunosuppression
1. Hau ML et a. Oncologist, 2022:27:971-981 PeerView.com
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Oncology Nursing Practice Forum
Case-Based Discussion: How to Establish
Best Nursing and Team-Based Practices
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Case-Based Discussion: How to Establish
Best Nursing and Team-Based Practices
Copyright © 2000-2024, PeerView
Oncology Nursing Practice Forum
Immune Checkpoint
Inhibitor-Related Pneumonitis
Beth Sandy, MSN, CRNP, FAPO
Thoracic Oncology Nurse Practitioner
Abramson Cancer Center
University of Pennsylvania
Philadelphia, Pennsylvania
Copyright © 2000-2024, PeerView
Immune Checkpoint
Inhibitor-Related Pneumonitis
Beth Sandy, MSN, CRNP, FAPO
Thoracic Oncology Nurse Practitioner
Abramson Cancer Center
University of Pennsylvania
Philadelphia, Pennsylvania
Copyright © 2000-2024, PeerView
Case: ICI-Related Pneumonitis
Q 71-year-old female with locally advanced NSCLC and a history of radiation to the chest
Q Now recurrent and metastatic; she was on pembrolizumab (single agent), 200 mg every 3 weeks
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Q 71-year-old female with locally advanced NSCLC and a history of radiation to the chest
Q Now recurrent and metastatic; she was on pembrolizumab (single agent), 200 mg every 3 weeks
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Case: ICI-Related Pneumonitis
71-year-old female with locally advanced NSCLC and a history of radiation to the chest
Now recurrent and metastatic; she was on pembrolizumab (single agent), 200 mg every 3 weeks
She was not having symptoms in July 2018, but scans indicate ground glass opacities (GGOs)
developing in the RUL (but subtle)
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71-year-old female with locally advanced NSCLC and a history of radiation to the chest
Now recurrent and metastatic; she was on pembrolizumab (single agent), 200 mg every 3 weeks
She was not having symptoms in July 2018, but scans indicate ground glass opacities (GGOs)
developing in the RUL (but subtle)
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Case: ICI-Related Pneumonitis!
71-year-old female with locally advanced NSCLC and a history of radiation to the chest
Now recurrent and metastatic; she was on pembrolizumab (single agent), 200 mg every 3 weeks
She was not having symptoms in July 2018, but scans indicate ground glass opacities (GGOs)
developing in the RUL (but subtle)
CT chest May 2018 S CT chest July 2018
1. Images provided courtesy ol Beth Sandy, MSN, CRNP, FAPO, PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
71-year-old female with locally advanced NSCLC and a history of radiation to the chest
Now recurrent and metastatic; she was on pembrolizumab (single agent), 200 mg every 3 weeks
She was not having symptoms in July 2018, but scans indicate ground glass opacities (GGOs)
developing in the RUL (but subtle)
CT chest May 2018 S CT chest July 2018
1. Images provided courtesy ol Beth Sandy, MSN, CRNP, FAPO, PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
Case: Pneumonitis!
AE Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
SEE ; Leteatenng
clinical or diagnostic STE ‘Severe symptoms; respiratory compromise;
Pneumonitis ‘observation only, pete O limiting self-care ADL; urgent intervention Death
venin Admin osgennaeaet dead eg
ral cas acheter. baton)
+ Now, in September 2018, she has
developed a minor cough, but she is not
SOB; oxygen saturation is 98% on RA
+ Radiographically, pneumonitis appears
to be increasing
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1. Images provided courtesy of Beth Sandy, MSN, CRNP, FAPO.
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AE Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
SEE ; Leteatenng
clinical or diagnostic STE ‘Severe symptoms; respiratory compromise;
Pneumonitis ‘observation only, pete O limiting self-care ADL; urgent intervention Death
venin Admin osgennaeaet dead eg
ral cas acheter. baton)
+ Now, in September 2018, she has
developed a minor cough, but she is not
SOB; oxygen saturation is 98% on RA
+ Radiographically, pneumonitis appears
to be increasing
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1. Images provided courtesy of Beth Sandy, MSN, CRNP, FAPO.
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Rates of Pneumonitis Indicated in Prescribing Information
Rate of
Pneumonitis in All Rate of Pneumonitis in NSCLC
Cancer Types
Pembrolizumab 3.4% 7% in NSCLC resected cohort
Nivolumab 3.1% 9% in NSCLC when given with ipilimumab
Atezolizumab 3.0% 3.8% in NSCLC resected cohort
Durvalumab 24% 18% in NSCLC post chemo/radiation
Cemiplimab 2.6% NR
+ In NSCLC, rate of pneumonitis is often higher than other disease sites
— One retrospective analysis! of 167 NSCLC patients receiving ICls reported that 13.2%
of patients developed pneumonitis, 4.2% of which experienced grade 3/4
1.ChoJY etal. Lung Cancer 2018:125:150-156 PeerView.com
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Rate of
Pneumonitis in All Rate of Pneumonitis in NSCLC
Cancer Types
Pembrolizumab 3.4% 7% in NSCLC resected cohort
Nivolumab 3.1% 9% in NSCLC when given with ipilimumab
Atezolizumab 3.0% 3.8% in NSCLC resected cohort
Durvalumab 24% 18% in NSCLC post chemo/radiation
Cemiplimab 2.6% NR
+ In NSCLC, rate of pneumonitis is often higher than other disease sites
— One retrospective analysis! of 167 NSCLC patients receiving ICls reported that 13.2%
of patients developed pneumonitis, 4.2% of which experienced grade 3/4
1.ChoJY etal. Lung Cancer 2018:125:150-156 PeerView.com
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© Pulmonary irAEs +.
Practice Ald
BDD} Preumonitis (more common with PD-1/PD-L1 inhibitors; 20%-30% mortality) ¿EAU
Report Assess Support
Rule out other causes: dass progression,
funerary mba een nie.
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Practice Ald
BDD} Preumonitis (more common with PD-1/PD-L1 inhibitors; 20%-30% mortality) ¿EAU
Report Assess Support
Rule out other causes: dass progression,
funerary mba een nie.
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Case: ICI-Related Pneumonitis
Let’s Discuss
Q Phneumonitis in this patient
- Surprisingly, only mildly symptomatic given the severity of the pneumonitis
seen on the chest CT
What is the grade of pneumonitis in this patient?
> Initially, grade 1, now grade 2 but mild
How would you manage this based on the latest guidelines?
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Let’s Discuss
Q Phneumonitis in this patient
- Surprisingly, only mildly symptomatic given the severity of the pneumonitis
seen on the chest CT
What is the grade of pneumonitis in this patient?
> Initially, grade 1, now grade 2 but mild
How would you manage this based on the latest guidelines?
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NCCN Guidelines for ICI-Related Pneumonitis Management!
Pulmonary Grading Management
Adverse = Consider holding immunotherapy]
Event(s) + Reassess in 1-2 weeks
Pulse oximetry (resting and with ambulation)
+ Consider chest CT with contrast
= Consider repeat chest CT in 4-6 weeks or as clinically indicated if patient develops symptoms
+ Invasive evaluation
ronsider pulmonary consultation — Consider bronchoscopy with BAL (send for institutional
+ Minimally invasive evaluation immunocompromised panel), and consider transbronchial
- Consider infections workup lung biopsy if clinically feasible to rule out progressive
> Nasal swab for potential viral malignancy or fungal infections
pathogens + Consider empiric broad-spectrum antibiotics (including
>> Sp lt (hand Sasi, So age fo ea plana) Ufo has no yet ba
fungal, and acid-fast bacili (AFB),
blood culture, and urine antigen
test (pneumococcus, legionella)
= Chest CT with contrast, and repeat
chest CT in 3-4 weeks + Ifno improvement after 48-72 hours of steroids, treat as grade 3
1 ps: en rpprtessonaephysiian_ol/pdlimmunctnerapy pt. PeerView.com
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Pulmonary Grading Management
Adverse = Consider holding immunotherapy]
Event(s) + Reassess in 1-2 weeks
Pulse oximetry (resting and with ambulation)
+ Consider chest CT with contrast
= Consider repeat chest CT in 4-6 weeks or as clinically indicated if patient develops symptoms
+ Invasive evaluation
ronsider pulmonary consultation — Consider bronchoscopy with BAL (send for institutional
+ Minimally invasive evaluation immunocompromised panel), and consider transbronchial
- Consider infections workup lung biopsy if clinically feasible to rule out progressive
> Nasal swab for potential viral malignancy or fungal infections
pathogens + Consider empiric broad-spectrum antibiotics (including
>> Sp lt (hand Sasi, So age fo ea plana) Ufo has no yet ba
fungal, and acid-fast bacili (AFB),
blood culture, and urine antigen
test (pneumococcus, legionella)
= Chest CT with contrast, and repeat
chest CT in 3-4 weeks + Ifno improvement after 48-72 hours of steroids, treat as grade 3
1 ps: en rpprtessonaephysiian_ol/pdlimmunctnerapy pt. PeerView.com
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NCCN Guidelines for ICI-Related Pneumonitis Management!
‘Assessment! ‘Management
Grading
7 Inpatient care
+ Pulmonary and infectious disease consultation
+ Minimally invasive evaluation
= Infectious workup
Consider that the patient may be immunocompromised
> Nasal swab for potential viral pathogens
> Sputum culture (including bacterial, fungal, and AFB), blood culture, and urine antigen test
(pneumococcus, legionella)
Severe (G3-4) > Consider cardiac evaluation to exclude cardiac causes for clinical presentation
pneumonitis + Invasive evaluation
- Bronchoscopy with BAL (send for institutional immunocompromised panel) if feasible to rule out infection
and malignant lung infiltration, and consider transbronchial lung biopsy if feasible and clinically indicated
+ Consider empiric broad-spectrum antibiotics (including coverage for atypical pathogens) if infection has not
et been fully excluded
= IV methylprednisolone 1-2 mg/kg/day, assess response within 48 hours and plan taper over 26 weeks
+ Consider adding any of the following if no improvement after 48 hours
— IV infliximab 5 mg/kg; a second dose may be repeated 14 days later at the discretion of the treating provider
-IvIG
— Mycophenolate mofetil 1-1.5 g twice daily and then taper in consultation with pulmonary service
1. ps www nen org/protessionals!physican_ols/pdtimmunotherapy at PeerView.com
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‘Assessment! ‘Management
Grading
7 Inpatient care
+ Pulmonary and infectious disease consultation
+ Minimally invasive evaluation
= Infectious workup
Consider that the patient may be immunocompromised
> Nasal swab for potential viral pathogens
> Sputum culture (including bacterial, fungal, and AFB), blood culture, and urine antigen test
(pneumococcus, legionella)
Severe (G3-4) > Consider cardiac evaluation to exclude cardiac causes for clinical presentation
pneumonitis + Invasive evaluation
- Bronchoscopy with BAL (send for institutional immunocompromised panel) if feasible to rule out infection
and malignant lung infiltration, and consider transbronchial lung biopsy if feasible and clinically indicated
+ Consider empiric broad-spectrum antibiotics (including coverage for atypical pathogens) if infection has not
et been fully excluded
= IV methylprednisolone 1-2 mg/kg/day, assess response within 48 hours and plan taper over 26 weeks
+ Consider adding any of the following if no improvement after 48 hours
— IV infliximab 5 mg/kg; a second dose may be repeated 14 days later at the discretion of the treating provider
-IvIG
— Mycophenolate mofetil 1-1.5 g twice daily and then taper in consultation with pulmonary service
1. ps www nen org/protessionals!physican_ols/pdtimmunotherapy at PeerView.com
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Case: ICI-Related Pneumonitis
Initially, the patient had grade 1 pneumonitis: continued treatment, given the absence
of symptoms,
Next CT scan: pneumonitis radiographically worse, and the patient had developed
a cough
— Stopped pembrolizumab and initiated prednisone at 1 mg/kg/d
(eg, 150 Ib = 68 kg; therefore, 60-70 mg of prednisone per day)
Responded well to prednisone and was able to restart pembrolizumab
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Initially, the patient had grade 1 pneumonitis: continued treatment, given the absence
of symptoms,
Next CT scan: pneumonitis radiographically worse, and the patient had developed
a cough
— Stopped pembrolizumab and initiated prednisone at 1 mg/kg/d
(eg, 150 Ib = 68 kg; therefore, 60-70 mg of prednisone per day)
Responded well to prednisone and was able to restart pembrolizumab
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Pearls for Managing Pneumonitis
+ Chest CT is important to evaluate for pneumonitis; CXR is not enough
+ Baseline pulse oximetry is important
+ SOB, dry cough, and hypoxia are the most common symptoms
+ Manage with high-dose prednisone
+ Frequent follow-up is recommended
+ Repeat chest CT prior to restarting treatment
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+ Chest CT is important to evaluate for pneumonitis; CXR is not enough
+ Baseline pulse oximetry is important
+ SOB, dry cough, and hypoxia are the most common symptoms
+ Manage with high-dose prednisone
+ Frequent follow-up is recommended
+ Repeat chest CT prior to restarting treatment
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Oncology Nursing Practice Forum
Immune Checkpoint
Inhibitor-Related Hepatitis
Marianne Davies, DNP, ACNP, AOCNP, FAAN
Program Manager Care Signature, Oncology
Oncology Nurse Practitioner
Yale Comprehensive Cancer Center & Smilow Cancer Center
Associate Professor
Yale School of Nursing
New Haven, Connecticut
Copyright © 2000-2024, PeerView
Immune Checkpoint
Inhibitor-Related Hepatitis
Marianne Davies, DNP, ACNP, AOCNP, FAAN
Program Manager Care Signature, Oncology
Oncology Nurse Practitioner
Yale Comprehensive Cancer Center & Smilow Cancer Center
Associate Professor
Yale School of Nursing
New Haven, Connecticut
Copyright © 2000-2024, PeerView
Case: ICI-Related Hepatitis
Q 62-year-old female patient presented to ED with dyspnea and hypoxia; KPS 90%
- CTA
> Bilateral pulmonary emboli — started on enoxaparin
» RML mass with hilar and mediastinal adenopathy; liver metastases
— Biopsy: NSCLC adenocarcinoma, no actionable mutations, PD-L1 10%
Q Treatment: carboplatin, paclitaxel, atezolizumab, and bevacizumab (IMpower150)'
Q Patient education
— Chemotherapy side effects: myelosuppression, metabolic abnormalities (renal and liver),
nausea, peripheral neuropathy
— Bevacizumab side effects: hypertension, bleeding
— Atezolizumab side effects: irAEs
1. Mis encata gowstudy NCTO2366143. PeerView.com
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Q 62-year-old female patient presented to ED with dyspnea and hypoxia; KPS 90%
- CTA
> Bilateral pulmonary emboli — started on enoxaparin
» RML mass with hilar and mediastinal adenopathy; liver metastases
— Biopsy: NSCLC adenocarcinoma, no actionable mutations, PD-L1 10%
Q Treatment: carboplatin, paclitaxel, atezolizumab, and bevacizumab (IMpower150)'
Q Patient education
— Chemotherapy side effects: myelosuppression, metabolic abnormalities (renal and liver),
nausea, peripheral neuropathy
— Bevacizumab side effects: hypertension, bleeding
— Atezolizumab side effects: irAEs
1. Mis encata gowstudy NCTO2366143. PeerView.com
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Case: ICI-Related Hepatitis
+ Diagnosis: metastatic NSCLC
+ Treatment: carboplatin, paclitaxel, atezolizumab, and bevacizumab (IMpower150)
+ Baseline labs:
Day WBC ANC AlkPh Tbili AST
Norm 4-10 1-11 0.4-1.3 9-122 <1.2 10-35 10-35
1 5.2 3.4 0.87 113 0.3 24 28
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+ Diagnosis: metastatic NSCLC
+ Treatment: carboplatin, paclitaxel, atezolizumab, and bevacizumab (IMpower150)
+ Baseline labs:
Day WBC ANC AlkPh Tbili AST
Norm 4-10 1-11 0.4-1.3 9-122 <1.2 10-35 10-35
1 5.2 3.4 0.87 113 0.3 24 28
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Case: ICI-Related Hepatitis
+ Diagnosis: metastatic NSCLC
+ Treatment: carboplatin, paclitaxel, atezolizumab, and bevacizumab (IMpower150)
+ AEs: transaminitis and neutropenia
Day WBC ANC AlkPh T. Bil ALT AST
Norm 4-10 1-11 0.4-1.3 9-122 <1.2 10-35 10-35
1 5.2 3.4 0.87 113 0.3 24 28
1 3.3 2.2 0.73 174 0.4
14 2.0 0.6 0.67 235 0.3
21 3.6 1.2 0.72 246 0.4
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+ Diagnosis: metastatic NSCLC
+ Treatment: carboplatin, paclitaxel, atezolizumab, and bevacizumab (IMpower150)
+ AEs: transaminitis and neutropenia
Day WBC ANC AlkPh T. Bil ALT AST
Norm 4-10 1-11 0.4-1.3 9-122 <1.2 10-35 10-35
1 5.2 3.4 0.87 113 0.3 24 28
1 3.3 2.2 0.73 174 0.4
14 2.0 0.6 0.67 235 0.3
21 3.6 1.2 0.72 246 0.4
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@ Hepatic irAEs EA
Practice Ald
levate Ss, hepatitis,
)D Elevated LFTs, hepatitis, ALF
o seruun»unsoun
o REA Report Assess Support
init uno of hepato run and cono
+ ASTALT>30S9xUN
Totti 1530 UN
ASALTAN =
gy Tot bain un
ASTÍALT>50200xULN
D : Total nn» 30-100: UN
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Practice Ald
levate Ss, hepatitis,
)D Elevated LFTs, hepatitis, ALF
o seruun»unsoun
o REA Report Assess Support
init uno of hepato run and cono
+ ASTALT>30S9xUN
Totti 1530 UN
ASALTAN =
gy Tot bain un
ASTÍALT>50200xULN
D : Total nn» 30-100: UN
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Case: ICI-Related Hepatitis
Diagnosis: metastatic NSCLC
- Liver metastases
Treatment: carboplatin, paclitaxel,
atezolizumab, and bevacizumab
(IMpower150)
AEs: transaminitis and neutropenia
Grading, evaluation, and management
— Grade 3 transaminitis
— Hepatitis and viral panel
- Gl-hepatology consult
- MRIMRCP of liver
Cycle 2: hold paclitaxel; pegfilgrastim
Long-term follow-up (section 4)
PeerView.com/XRX827
Day WBC ANC AlkPh
Norm 4-10
1 5.2
T 3.3
14 2.0
21 3.6
28 44
35 29.2
42 45
1-11
3.4
2.2
0.6
1.2
29
24.5
2.8
9-122
113
174
235
246
258
294
280
AS
<1.2 10-35 10-35
03 24 28
0.4
0.3
0.4
0.5
0.4
0.3
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Diagnosis: metastatic NSCLC
- Liver metastases
Treatment: carboplatin, paclitaxel,
atezolizumab, and bevacizumab
(IMpower150)
AEs: transaminitis and neutropenia
Grading, evaluation, and management
— Grade 3 transaminitis
— Hepatitis and viral panel
- Gl-hepatology consult
- MRIMRCP of liver
Cycle 2: hold paclitaxel; pegfilgrastim
Long-term follow-up (section 4)
PeerView.com/XRX827
Day WBC ANC AlkPh
Norm 4-10
1 5.2
T 3.3
14 2.0
21 3.6
28 44
35 29.2
42 45
1-11
3.4
2.2
0.6
1.2
29
24.5
2.8
9-122
113
174
235
246
258
294
280
AS
<1.2 10-35 10-35
03 24 28
0.4
0.3
0.4
0.5
0.4
0.3
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Oncology Nursing Practice Forum
Immune Checkpoint
Inhibitor-Related Myocarditis
Matthew A. Gubens, MD, MS, FASCO
Division of Hematology/Oncology
Department of Medicine
University of California San Francisco
Professor of Medicine
Medical Director, Thoracic Medical Oncology 8
we
bw
San Francisco, California =
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Immune Checkpoint
Inhibitor-Related Myocarditis
Matthew A. Gubens, MD, MS, FASCO
Division of Hematology/Oncology
Department of Medicine
University of California San Francisco
Professor of Medicine
Medical Director, Thoracic Medical Oncology 8
we
bw
San Francisco, California =
Copyright © 2000-2024, Peerview
Case: ICI-Related Myocarditis
Q 74-year-old male with stage IV NSCLC; started first cycle of chemotherapy and pembrolizumab
3 weeks ago
— PMH: HTN, osteoarthritis, CVA, stage Ill melanoma s/p resection 8 years ago, another radical
resection last year; wide local excision 6 weeks ago
Q Presents to urgent care for cold symptoms
— 1 week ago: congestion, cough
— 2 days ago: diffuse myalgias in shoulder, back, thighs; muscles feel “overworked”
and tender despite sedentary lifestyle; general weakness
Endorses SOB with physical activity, especially when climbing stairs
ROS notable for leg swelling, back pain, neck pain, dizziness, HA
CV: rhythm irregular; 1+ pitting edema in bilateral LEs
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Q 74-year-old male with stage IV NSCLC; started first cycle of chemotherapy and pembrolizumab
3 weeks ago
— PMH: HTN, osteoarthritis, CVA, stage Ill melanoma s/p resection 8 years ago, another radical
resection last year; wide local excision 6 weeks ago
Q Presents to urgent care for cold symptoms
— 1 week ago: congestion, cough
— 2 days ago: diffuse myalgias in shoulder, back, thighs; muscles feel “overworked”
and tender despite sedentary lifestyle; general weakness
Endorses SOB with physical activity, especially when climbing stairs
ROS notable for leg swelling, back pain, neck pain, dizziness, HA
CV: rhythm irregular; 1+ pitting edema in bilateral LEs
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© Cardiac irAEs EA
Practice Ald
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Cardiovascular Symptom Cluster’
Myasthenia gravis
+ Fatigable muscle weakness
+ Ophthalmoparesis and ptosis
+ Bulbar involvement
+ Respiratory failure
Myositis
+ Myalgia and absence
of muscle fatigability
+ Limb-girdle pattern with
proximal limbs weakness
Myocarditis/myositis/myasthenia overlap syndrome
+ Early onset (median after one dose)
+ Extremely rare (incidence <0.1%)
+ High mortality rate (57%)
1. Raschi et al. Drug Sal. 202346 818-833. 2. Taj K. eda M. Front Cardiovasc Med, 2019:83. 3, Van Buren ea. JAMA Netw Open. 2023:8:e2340895.
4. Mahmood SS et a. J Am Coll Corda! 2010,71:1755-1768 5 Palaskas Net a. Am Heart Assoc. 2020.9 013757 ne
$. Wang DY et al JAMA Oncol 20184: 1721-1728, PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
Myasthenia gravis
+ Fatigable muscle weakness
+ Ophthalmoparesis and ptosis
+ Bulbar involvement
+ Respiratory failure
Myositis
+ Myalgia and absence
of muscle fatigability
+ Limb-girdle pattern with
proximal limbs weakness
Myocarditis/myositis/myasthenia overlap syndrome
+ Early onset (median after one dose)
+ Extremely rare (incidence <0.1%)
+ High mortality rate (57%)
1. Raschi et al. Drug Sal. 202346 818-833. 2. Taj K. eda M. Front Cardiovasc Med, 2019:83. 3, Van Buren ea. JAMA Netw Open. 2023:8:e2340895.
4. Mahmood SS et a. J Am Coll Corda! 2010,71:1755-1768 5 Palaskas Net a. Am Heart Assoc. 2020.9 013757 ne
$. Wang DY et al JAMA Oncol 20184: 1721-1728, PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
Case: ICI-Related Myocarditis
Q Cardiology consult and ECG; CMP, CK, troponin | drawn
AST 762 U/L (normal 16-40 U/L), ALT 376 U/L (normal 5-60 U/L)
Troponin | 8.12 ng/mL (normal 0.00-0.03 ng/mL), BNP 162 (>100 = CHF)
CK 8,831 U/L (normal 20-200 U/L), aldolase 121 U/L (normal 1.2-7.6 U/L)
ECG: atrial fibrillation with RVR
OD Methylprednisolone 1,000 mg IV daily and heparin drip initiated
- Telemetry, serial ECG, troponins; ECHO: low normal EF 53%
— Discussion of clinical trial for abatacept for immune-related myocarditis
= Troponin worsens despite 4 days of high-dose corticosteroids Next steps?
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Q Cardiology consult and ECG; CMP, CK, troponin | drawn
AST 762 U/L (normal 16-40 U/L), ALT 376 U/L (normal 5-60 U/L)
Troponin | 8.12 ng/mL (normal 0.00-0.03 ng/mL), BNP 162 (>100 = CHF)
CK 8,831 U/L (normal 20-200 U/L), aldolase 121 U/L (normal 1.2-7.6 U/L)
ECG: atrial fibrillation with RVR
OD Methylprednisolone 1,000 mg IV daily and heparin drip initiated
- Telemetry, serial ECG, troponins; ECHO: low normal EF 53%
— Discussion of clinical trial for abatacept for immune-related myocarditis
= Troponin worsens despite 4 days of high-dose corticosteroids Next steps?
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ICI-Related Myocarditis
+ Chest CT is important to evaluate for pneumonitis; CXR is not enough
+ Baseline pulse oximetry is important
+ SOB, dry cough, and hypoxia are the most common symptoms
+ Manage with high-dose prednisone
+ Frequent follow-up is recommended
+ Repeat chest CT prior to restarting treatment
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+ Chest CT is important to evaluate for pneumonitis; CXR is not enough
+ Baseline pulse oximetry is important
+ SOB, dry cough, and hypoxia are the most common symptoms
+ Manage with high-dose prednisone
+ Frequent follow-up is recommended
+ Repeat chest CT prior to restarting treatment
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ICI-Related Myocarditis:
A Rare, Insidious, Deadly, and Early irAE!
Weakness, muscle pain, dyspnea,
Incidence: : PER ge elena
High mortality:
Median onset:
0.04%-1.14% palpitations, fatigue, edema > Progressing
to life-threatening arrhythmia/shock
25%-50%
~30 days from start of ICI
Workup
+ Immediate cardiology consult
* Troponin | (f in 94% of cases), BNP, CK
+ CXR, ECG, ECHO (| in 51% of cases), cardiac MRI
Management
+ Start steroids ASAP: methylprednisolone pulse 1,000 mg IV daily x 3 days > 1 mg/kg prednisone PO,
methylprednisolone IV
— Ifno improvement in 24-48 hours, treat with secondary immunosuppression
> Abatacept, mycophenolate, IVIG, ATG, plasmapheresis
> Alemtuzumab (restricted access in US)
> Infliximab (CV risk; use extreme caution with |LVEF) .
1. Palaskas N et al. J Am Heart Assoc: 202096013757. PeerView.com
PeerView.com/XRX827 Copyright © 2000-2024, PeerView
A Rare, Insidious, Deadly, and Early irAE!
Weakness, muscle pain, dyspnea,
Incidence: : PER ge elena
High mortality:
Median onset:
0.04%-1.14% palpitations, fatigue, edema > Progressing
to life-threatening arrhythmia/shock
25%-50%
~30 days from start of ICI
Workup
+ Immediate cardiology consult
* Troponin | (f in 94% of cases), BNP, CK
+ CXR, ECG, ECHO (| in 51% of cases), cardiac MRI
Management
+ Start steroids ASAP: methylprednisolone pulse 1,000 mg IV daily x 3 days > 1 mg/kg prednisone PO,
methylprednisolone IV
— Ifno improvement in 24-48 hours, treat with secondary immunosuppression
> Abatacept, mycophenolate, IVIG, ATG, plasmapheresis
> Alemtuzumab (restricted access in US)
> Infliximab (CV risk; use extreme caution with |LVEF) .
1. Palaskas N et al. J Am Heart Assoc: 202096013757. PeerView.com
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ICI-Related Major Adverse Cardiac Events (ICI-MACEs)
ICI-MACEs: myocarditis, NSTEMIs/STEMIs, CHF, pericardial disorders, dysrhythmias, cardiac arrest
Pooled analysis of NCI-Cancer Therapy Evaluation Program!
+ N = 6,925 patients on anti-PD-L1-based therapies
— 48% (n = 3,354) received anti-PD-L1 monotherapy
- 0.6% of all patients (n = 40) qualified as ICI-MACEs
— Incidence of ICI-MACEs higher with involvement seen in 65%
of cases of ICHMACEs
Concurrent multisystem
> Targeted therapy combinations (2.1% vs 0.9%)
> Any combination therapy (0.36% vs 0.15%)
— Myocarditis: 45% (n = 18) of ICI-MACEs
> 83% (n= 15) had 21 noncardiac irAE associated with myocarditis
> All 4 patients who died had concurrent myositis
Tiew:
1. Nagash AR et a. J Clin Oncol. 2022:40:3439-3482. PeerView.com
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ICI-MACEs: myocarditis, NSTEMIs/STEMIs, CHF, pericardial disorders, dysrhythmias, cardiac arrest
Pooled analysis of NCI-Cancer Therapy Evaluation Program!
+ N = 6,925 patients on anti-PD-L1-based therapies
— 48% (n = 3,354) received anti-PD-L1 monotherapy
- 0.6% of all patients (n = 40) qualified as ICI-MACEs
— Incidence of ICI-MACEs higher with involvement seen in 65%
of cases of ICHMACEs
Concurrent multisystem
> Targeted therapy combinations (2.1% vs 0.9%)
> Any combination therapy (0.36% vs 0.15%)
— Myocarditis: 45% (n = 18) of ICI-MACEs
> 83% (n= 15) had 21 noncardiac irAE associated with myocarditis
> All 4 patients who died had concurrent myositis
Tiew:
1. Nagash AR et a. J Clin Oncol. 2022:40:3439-3482. PeerView.com
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Myocarditis and Myositis/Myasthenia Gravis
Overlap Syndrome
+ Myositis/myasthenia gravis can occur with myocarditis
— Potential for life-threatening respiratory paralysis, death
+ Patient symptoms and characteristics (systematic review of 60 patients)!
— Fatigue (80%), muscle weakness (78%); average CK 9,645 IU/L
— Arrhythmia (67%), reduced ejection fraction (18%)
— High mortality (60%) in hospital
+ Treatment
— High-dose corticosteroids
— Variable secondary agents: IVIG and plasmapheresis common
as autoantibody-directed therapies
Incidence unknown Suspect and workup for myositis/MG in all
(30%-40% of myocarditis cases?) patients with ICI-related myocarditis
fiéw.
1. Pathak Ret al. Oncologist 2021:26:1052-1081 PeerView.com
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Overlap Syndrome
+ Myositis/myasthenia gravis can occur with myocarditis
— Potential for life-threatening respiratory paralysis, death
+ Patient symptoms and characteristics (systematic review of 60 patients)!
— Fatigue (80%), muscle weakness (78%); average CK 9,645 IU/L
— Arrhythmia (67%), reduced ejection fraction (18%)
— High mortality (60%) in hospital
+ Treatment
— High-dose corticosteroids
— Variable secondary agents: IVIG and plasmapheresis common
as autoantibody-directed therapies
Incidence unknown Suspect and workup for myositis/MG in all
(30%-40% of myocarditis cases?) patients with ICI-related myocarditis
fiéw.
1. Pathak Ret al. Oncologist 2021:26:1052-1081 PeerView.com
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Case: ICI-Related Myocarditis
Q = Myasthenia gravis workup (day 4): AChR antibodies negative
— Limited adduction and abduction of eyelids (day 5), progressively worsened; maximal inspiratory
pressure declined from 35 to 22
Q High-dose steroids continued; secondary agent timeline
— Mycophenolate (day 3)
- IMIG and abatacept (both given day 5-6; off trial due to ineligibility)
» Day 5-11: worsening respiratory status > intubated (day 11)
» Cardiac MRI (day 6): consistent with myocarditis
- ATG (day 10) > hypotensive/shock secondary to CRS vs sepsis Died on day
» Day 11: pressor support, transcutaneous pacing > tocilizumab 15 after initial
+ Patient worsened with inability to wean off vasopressors due to hypotension presentation
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Q = Myasthenia gravis workup (day 4): AChR antibodies negative
— Limited adduction and abduction of eyelids (day 5), progressively worsened; maximal inspiratory
pressure declined from 35 to 22
Q High-dose steroids continued; secondary agent timeline
— Mycophenolate (day 3)
- IMIG and abatacept (both given day 5-6; off trial due to ineligibility)
» Day 5-11: worsening respiratory status > intubated (day 11)
» Cardiac MRI (day 6): consistent with myocarditis
- ATG (day 10) > hypotensive/shock secondary to CRS vs sepsis Died on day
» Day 11: pressor support, transcutaneous pacing > tocilizumab 15 after initial
+ Patient worsened with inability to wean off vasopressors due to hypotension presentation
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Myocarditis and Myositis/Myasthenia Gravis
Overlap Syndrome: A Cautionary Tale
ICI-MACEs, myocardi myositis/myasthenia gravis overlap syndrome
> early, poorly recognized irAEs; may result in delayed diagnosis, treatment
How to improve outcomes Challenges and unknowns
+ Baseline cardiac monitoring
+ Improve awareness of nonspecific symptoms + Past/family history of cardiac disease
as red flags early after starting ICI therapy + Prediction of those at highest risk
+ Earlier identification, intervention
+ Consider myositis and myasthenia gravis Education is key
for any case of ICI-related myocarditis
Proactive risk/benefit discussion
+ Clinical trials to evaluate efficacy with baseline risk factors
of secondary immunosuppression ICI therapy carries 1% risk of death;
not a benign treatment
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Overlap Syndrome: A Cautionary Tale
ICI-MACEs, myocardi myositis/myasthenia gravis overlap syndrome
> early, poorly recognized irAEs; may result in delayed diagnosis, treatment
How to improve outcomes Challenges and unknowns
+ Baseline cardiac monitoring
+ Improve awareness of nonspecific symptoms + Past/family history of cardiac disease
as red flags early after starting ICI therapy + Prediction of those at highest risk
+ Earlier identification, intervention
+ Consider myositis and myasthenia gravis Education is key
for any case of ICI-related myocarditis
Proactive risk/benefit discussion
+ Clinical trials to evaluate efficacy with baseline risk factors
of secondary immunosuppression ICI therapy carries 1% risk of death;
not a benign treatment
PeerView.com
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Oncology Nursing Practice Forum
Immune Checkpoint
Inhibitor-Related Nephritis
Marianne Davies, DNP, ACNP, AOCNP, FAAN
Program Manager Care Signature, Oncology
Oncology Nurse Practitioner
Yale Comprehensive Cancer Center & Smilow Cancer Center
Associate Professor
Yale School of Nursing
New Haven, Connecticut
Copyright © 2000-2024, PeerView
Immune Checkpoint
Inhibitor-Related Nephritis
Marianne Davies, DNP, ACNP, AOCNP, FAAN
Program Manager Care Signature, Oncology
Oncology Nurse Practitioner
Yale Comprehensive Cancer Center & Smilow Cancer Center
Associate Professor
Yale School of Nursing
New Haven, Connecticut
Copyright © 2000-2024, PeerView
Case: ICI-Related Nephritis
Q 65-year-old male is receiving carboplatin/pemetrexed and cemiplimab for 1L treatment
of metastatic nonsquamous NSCLC,
Q Atweek 10, after 3 cycles, routine labs show a grade 2 serum creatinine elevation
— Current sCr: 2.0 mg/dL
— Baseline sCr: 0.8 mg/dL
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Q 65-year-old male is receiving carboplatin/pemetrexed and cemiplimab for 1L treatment
of metastatic nonsquamous NSCLC,
Q Atweek 10, after 3 cycles, routine labs show a grade 2 serum creatinine elevation
— Current sCr: 2.0 mg/dL
— Baseline sCr: 0.8 mg/dL
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ICI-Related Nephritis: Recommended Approach
1. Continue both carboplatin/pemetrexed
and cemiplimab
Rationale
Both carboplatin/pemetrexed and ICIs can cause
kidney injury, although later onset suggests ICI as
2. | Hold both carboplatin/pemetrexed
and cel b
causative agent
3. Dose reduce both carboplatin/pemetrexed Experts recommend holding both chemo and ICI to
and cemiplimab help determine causative agent
+ IfsCr elevation clears before next cycle: likely caused
4. Permanently discontinue both carboplatin/pemetrexed by carboplatinipemetrexed; manage with CT} hold and
hs dose reduction
and cemiplimab 7
+ If Cr elevation persists/worsens: likely caused by the
F ICI; manage with ICI hold and steroids
5. Uncertain
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1. Continue both carboplatin/pemetrexed
and cemiplimab
Rationale
Both carboplatin/pemetrexed and ICIs can cause
kidney injury, although later onset suggests ICI as
2. | Hold both carboplatin/pemetrexed
and cel b
causative agent
3. Dose reduce both carboplatin/pemetrexed Experts recommend holding both chemo and ICI to
and cemiplimab help determine causative agent
+ IfsCr elevation clears before next cycle: likely caused
4. Permanently discontinue both carboplatin/pemetrexed by carboplatinipemetrexed; manage with CT} hold and
hs dose reduction
and cemiplimab 7
+ If Cr elevation persists/worsens: likely caused by the
F ICI; manage with ICI hold and steroids
5. Uncertain
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© Renal irAEs EA
Practice Ald
> sons xro CRE
Report Assess Support
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Practice Ald
> sons xro CRE
Report Assess Support
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Oncology Nursing Practice Forum
Immune Checkpoint Inhibitor-Related Uveitis
Beth Sandy, MSN, CRNP, FAPO
Thoracic Oncology Nurse Practitioner
Abramson Cancer Center
University of Pennsylvania
Philadelphia, Pennsylvania
Copyright © 2000-2024, PeerView
Immune Checkpoint Inhibitor-Related Uveitis
Beth Sandy, MSN, CRNP, FAPO
Thoracic Oncology Nurse Practitioner
Abramson Cancer Center
University of Pennsylvania
Philadelphia, Pennsylvania
Copyright © 2000-2024, PeerView
Case: ICI-Related Uveitis’
Q = 75-year-old male with a history of metastatic NSCLC
(adenocarcinoma, no actionable biomarkers, PD-L1 0%)
Treated with 4 cycles of pemetrexed/carboplatin
and pembrolizumab with a good response and then
6 cycles of maintenance pemetrexed and pembrolizumab
Presents for cycle 7 of maintenance pemetrexed
and pembrolizumab: bilateral eyes are red in sclera,
no drainage, very sensitive to light, painful at times,
distorted vision
1. Provided courtesy of Beth Sandy, MSN, CRNP, FAPO. PeerVie
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Q = 75-year-old male with a history of metastatic NSCLC
(adenocarcinoma, no actionable biomarkers, PD-L1 0%)
Treated with 4 cycles of pemetrexed/carboplatin
and pembrolizumab with a good response and then
6 cycles of maintenance pemetrexed and pembrolizumab
Presents for cycle 7 of maintenance pemetrexed
and pembrolizumab: bilateral eyes are red in sclera,
no drainage, very sensitive to light, painful at times,
distorted vision
1. Provided courtesy of Beth Sandy, MSN, CRNP, FAPO. PeerVie
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Uvea: The Middle Layer of the Wall of the Eye
The uvea has 3 main components!
1. The choroid (tissue layer filled with blood vessels)
2. The ciliary body (ring of tissue that contains
muscles that change the shape of the lens and
makes the clear fluid that fills the space between
the cornea and the iris)
3. The iris (colored part of the eye); also called
the uveal tract
1. aps ww cancer goVpublcaonsditonaries/cancertermside1uvea. Image provided courtesy ot NCI Dictionaries. PeerView.com
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The uvea has 3 main components!
1. The choroid (tissue layer filled with blood vessels)
2. The ciliary body (ring of tissue that contains
muscles that change the shape of the lens and
makes the clear fluid that fills the space between
the cornea and the iris)
3. The iris (colored part of the eye); also called
the uveal tract
1. aps ww cancer goVpublcaonsditonaries/cancertermside1uvea. Image provided courtesy ot NCI Dictionaries. PeerView.com
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© Ocular irAEs EA
Practice Ald
> Uveitis, iritis, sicca, conjunctivitis
Report Assess Support
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Practice Ald
> Uveitis, iritis, sicca, conjunctivitis
Report Assess Support
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NCCN Guidelines for ICI-Related Uveitis Management!
Ocular Assessment! Management Based on Collaboration With Ophthalmology
Adverse Grading
Event(s)
+ Hold immunotherapy to observe for worsening
uveitis; if uveitis is stable on topical therapy,
Anterior consider restarting immunotherapy in discussion
or intermediate with ophthalmology
uveitis (G1 or G2) Treatment guided by ophthalmology to include
ophthalmic + systemic prednisone/IV
+ Ophthalmology evaluation
and management
essential with vision
testing to include
methylprednisolone
Vision ake a Posterior Hold immunotherapy
changes pls ly: Treatment guided by ophthalmology to include
Mesa ophthalmic and systemic prednisone/IV
methylprednisolone
Pupil size, shape,
and reactivity
+ Anterior vs posterior uveitis
+ Treatment with topical steroids for anterior uveitis
1. ps ww nen org/protesionas/pysican_Is/palimmunotherapy pat PeerView.com
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Ocular Assessment! Management Based on Collaboration With Ophthalmology
Adverse Grading
Event(s)
+ Hold immunotherapy to observe for worsening
uveitis; if uveitis is stable on topical therapy,
Anterior consider restarting immunotherapy in discussion
or intermediate with ophthalmology
uveitis (G1 or G2) Treatment guided by ophthalmology to include
ophthalmic + systemic prednisone/IV
+ Ophthalmology evaluation
and management
essential with vision
testing to include
methylprednisolone
Vision ake a Posterior Hold immunotherapy
changes pls ly: Treatment guided by ophthalmology to include
Mesa ophthalmic and systemic prednisone/IV
methylprednisolone
Pupil size, shape,
and reactivity
+ Anterior vs posterior uveitis
+ Treatment with topical steroids for anterior uveitis
1. ps ww nen org/protesionas/pysican_Is/palimmunotherapy pat PeerView.com
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Case: ICI-Related Uveitis
Patient seen and evaluated by ophthalmology urgently
Started on prednisolone acetate (Pred Forte) eye drops every 6 hours with almost
immediate relief
Was able to taper down to every 12 hours in 1 week, and then one week later, only used
them PRN and had a full recovery
Resumed on pembrolizumab for 2 more cycles without recurrence of uveitis
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Patient seen and evaluated by ophthalmology urgently
Started on prednisolone acetate (Pred Forte) eye drops every 6 hours with almost
immediate relief
Was able to taper down to every 12 hours in 1 week, and then one week later, only used
them PRN and had a full recovery
Resumed on pembrolizumab for 2 more cycles without recurrence of uveitis
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irAE Treatment and Management: Key Takeaways
+ Nurses are integral to the monitoring of irAEs
Persistent grade 2 irAEs and grade 3 or 4 irAEs are treated with corticosteroids
+ Use of standardized algorithms for AE monitoring and management is beneficial
Early discontinuation of steroids may increase the risk of relapse or progression
of symptoms
Tapering of steroids should be carried out under the direct supervision
of a healthcare provider
Reinitiation of ICI may be possible with optimal management
— Decision to restart ICI is not always clear
Establishing a team-based, patient-centered care model promotes
patient satisfaction and can lead to improved treatment outcomes
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+ Nurses are integral to the monitoring of irAEs
Persistent grade 2 irAEs and grade 3 or 4 irAEs are treated with corticosteroids
+ Use of standardized algorithms for AE monitoring and management is beneficial
Early discontinuation of steroids may increase the risk of relapse or progression
of symptoms
Tapering of steroids should be carried out under the direct supervision
of a healthcare provider
Reinitiation of ICI may be possible with optimal management
— Decision to restart ICI is not always clear
Establishing a team-based, patient-centered care model promotes
patient satisfaction and can lead to improved treatment outcomes
PeerView.com
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