Opportunity Knocks in AML: Guidance on Achieving Truly Personalized Care in Challenging Populations with Modern Therapeutics

Co-Chairs, Naval Daver, MD, and Tapan Kadia, MD, prepared useful Practice Aids pertaining to acute myeloid leukemia for this CME/MOC/NCPD/CPE activity titled “Opportunity Knocks in AML: Guidance on Achieving Truly Personalized Care in Challenging Populations with Modern Therapeutics.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/NCPD/CPE information, and to apply for credit, please visit us at https://bit.ly/3RQYjFU. CME/MOC/NCPD/CPE credit will be available until October 5, 2025.

1. NSCLC Treatment Algorithm
1

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Stage and workup based on stage
• cT1abc, N0: PFT, bronch, mediastinal staging, PET
• cT2a-4, N0-3, M0-1: PFT, bronch, mediastinal staging, PET, brain MRI, and biomarker/mutation testing
Surgical candidate?
Lobectomy
(preferred)
or
segmentectomy/
wedge resection
(in select cases)
SBRT
or
conventionally
fractionated RT
Surgical resection
Test for PD-L1 status,
EGFR mutations,
and ALK rearrangements
Surgical resection
T1
N0
M0
Operable disease
Yes
Yes
No
No
Multidisciplinary discussion for
neoadjuvant candidacy
T1–2, N1–2, M0
T3–4, N0–1, M0
Neoadjuvant
chemoimmunotherapy
Neoadjuvant portion of perioperative immunotherapy
Nivolumab + platinum-based
chemotherapy x 3 cycles
CheckMate -816: Nivo + chemo vs
chemo (see FDA approval)
mEFS: 31.6 vs 20.8 mo (HR, 0.63)
Pembrolizumab + platinum-containing chemotherapy x 4 cycles as
neoadjuvant
KEYNOTE-671: Pembro + chemo vs placebo + chemo (neoadjuvant) / pembro
vs placebo (adjuvant) (see FDA approval)
mOS: not reached vs 52.4 mo; mEFS: not reached vs 17 mo
Adjuvant chemotherapy
Platinum-based chemotherapy
LACE Meta-analysis: 5-y OS improvement of 5.4% vs no chemo
Atezolizumab x 16 cycles
Stage II-IIIA, PD-L1 ≥1% (see FDA approval)
Atezolizumab x 16 cycles
IMpower010: Atezo vs BSC
mDFS: NR vs 35.3 mo (HR, 0.66)
Pembrolizumab x 1 y
Stage IB (T2a ≥4 cm), II, or IIIA, regardless
of PD-L1 expression (see FDA approval)
Pembrolizumab x 1 y
PEARLS/KEYNOTE-091: Pembro vs placebo
mDFS: 53.6 vs 42.0 mo (HR, 0.76)
Adjuvant EGFR-targeted therapy
Osimertinib x 3 y
ADAURA: Osimertinib vs placebo
2-y DFS (stage II-IIIA): 90% vs 44% (HR, 0.17)
NSCLC treatment algorithm
Stage IB-IIIA
(resectable)Stage IA
Surgical resection
Adjuvant portion of perioperative immunotherapy
Pembrolizumab, up to 13 cycles
KEYNOTE-671: Pembro + chemo vs placebo + chemo (neoadjuvant) /
pembro vs placebo (adjuvant) (see FDA approval) 
mOS: not reached vs 52.4 mo; mEFS: not reached vs 17 mo
Durvalumab + platinum-containing chemotherapy
AEGEAN: Durva + chemo vs placebo, followed by adjuvant durva vs
placebo (see FDA approval)
EFS: not reached vs 25.9 mo; pCR: 17% vs 4.3%
Yes
Adjuvant ALK-targeted therapy
Alectinib x 24 mo
ALINA: Alectinib vs chemo
mDFS: NR vs 41.3 mo
Adjuvant immunotherapy (stage II-IIIA)
ALK rearrangement
EGFR ex19del/ex21 L858R
EGFR ex19del/
ex21 L858R

2. Stage IIIA (unresectable) or IIIB/C
Definitive chemoradiation → durvalumab
Concurrent platinum-based chemotherapy and radiation with
consolidation durvalumab
PACIFIC: Durvalumab vs placebo
mPFS: 16.8 vs 5.6 mo (HR, 0.52)
BRAF V600E
Dabrafenib + trametinib
a
BRF113928: Dabrafenib + trametinib single arm
ORR: 64% (95% CI, 46-79)
Encorafenib + binimetinib
a
PHAROS: Encorafenib + binimetinib single arm (see FDA approval)
Treatment-naïve patients, ORR: 75% (95% CI, 62-85); mDOR: NE (95% CI, 23.1-NE)
Previously treated patients, ORR: 46% (95% CI, 30-63); mDOR: 16.7 mo (95% CI, 7.4-NE)
Vemurafenib
AcSé: Vemurafenib single arm
ORR: 45%; mPFS: 5.2 mo; OS: 10 mo
2L: KRAS G12C
Sotorasib
CodeBreaK100: Sotorasib single arm
ORR: 37.1% (95% CI, 29- 46); mPFS: 6.8 mo
Adagrasib
K RY STA L-1: Adagrasib single arm (see FDA approval)
ORR: 43% (95% CI, 34-53); mDOR: 8.5 mo
ALK
Alectinib
a

ALEX: Alectinib vs crizotinib
1-y PFS: 68.4% vs 48.7% (HR, 0.47)
Brigatinib
a
ALTA-1L: Brigatinib vs crizotinib
mPFS: 24 vs 11.1 mo (HR, 0.48)
Lorlatinib
a
CROWN: Lorlatinib vs crizotinib
mPFS: NR vs 9.3 mo (HR, 0.28); 1-y PFS: 78% vs 39%
Ceritinib
ASCEND-4: Ceritinib vs chemo
mPFS: 16.6 vs 8.1 mo (HR, 0.55)
Crizotinib
PROFILE 1007: Crizotinib vs chemo
mPFS: 7.7 vs 3 mo (HR, 0.49)
NTRK
Larotrectenib
a

NCT02122913/SCOUT/NAVIGATE : Larotrectenib single arm (see FDA approval)
ORR: 75% according to independent review and 80% according to investigator assessment
Entrectinib
a
ALKA/STARTRK: Entrectinib single arm (see FDA approval)
ORR: 70% (NSCLC)
Repotrectinib
TRIDENT-1: Repotrectinib in TKI naïve and TKI pretreated (see FDA approval)
ORR: 58% TKI naïve and 50% TKI pretreated
RET
EGFR S768I, L861Q, and/or G719X
Selpercatinib
a
LIBRETTO-001: Selpercatinib single arm (see FDA approval)
ORR: 64%; mDOR: 17.5 mo
Pralsetinib
a
ARROW: Pralsetinib single arm (see FDA approval)
Treatment-naïve patients, ORR: 78% (95% CI, 68-85); mDOR: 13.4 mo (95% CI, 9.4-23.1)
Previously treated patients, ORR: 63% (95% CI, 54-71); mDOR: 38.8 mo (95% CI, 14.8-NE)
Cabozantinib
NCT01639508: Cabozantinib single arm
ORR: 28%
Osimertinib
a
FLAURA: Osimertinib vs erlotinib/gefitinib
mPFS: 18.9 vs 10.2 mo (HR, 0.46)
Erlotinib
EU RTAC: Erlotinib vs chemo
mPFS: 9.7 vs 5.2 mo (HR, 0.37)
Afatinib
a
LUX-Lung 3: Afatinib vs cis/pemetrexed
mPFS: 13.6 vs 6.9 mo (HR, 0.47)
Gefitinib
IFUM: Gefitinib single arm
mPFS: 9.7 mo
Dacomitinib
ARCHER 1050: Dacomitinib vs gefitinib
mOS: 34.1 vs 27 mo (HR, 0.75)
Amivantamab + carboplatin + pemetrexed (nonsquamous)
MARIPOSA-2: Amivantamb + chemo ± lazertinib vs chemo
mPFS: 6.3, 8.3 vs 4.2 mo (HR, 0.48, 0.44); ORR: 64%, 63% vs 36% (P < .001 for both)
EGFR (ex20)
Amivantamab
CHRYSALIS: Amivantamab single arm
CBR: 74% (95%CI, 63-83); mPFS: 8.3 mo
Amivantamb + carboplatin + pemetrexed (nonsquamous)
a
PAPILLON: Amivantamab + chemo vs chemo
mPFS: 11.4 vs 6.7 mo (HR, 0.4); ORR: 73% vs 47%
ROS1
Crizotinib
a
PROFILE 1001: Crizotinib single arm
ORR: 72% (95% CI, 58-84)
Entrectinib
a
ALK A & STARTRK: Entrectinib single arm
ORR: 67.1%; mPFS: 19 mo
Ceritinib
YONSEI: Ceritinib single arm
ORR: 67% (95% CI, 48-81)
Repotrectinib
a
TRIDENT-1: Repotrectinib single arm (see FDA approval)
ROS1 TKI-naïve patients, ORR: 79% (95% CI, 68-88); mDOR: 34.1 mo (95% CI, 25.6-NE)
Prior ROS1 inhibitor, ORR: 38% (95% CI, 25 -52); mDOR: 14.8 mo (95% CI, 7.6-NE)
Lorlatinib
NCT01970865: Lorlatinib single arm
ROS TKI-naïve patients, ORR: 62%; Crizotinib pre-treated patients, ORR: 35%
EGFR (ex19 del or L858R)
Osimertinib
a
FLAURA: Osimertinib vs erlotinib/gefitinib
mPFS: 18.9 vs 10.2 mo (HR, 0.46)
Osimertinib + pemetrexed + cisplatin/carboplatin
FLAURA2: Osimertinib + chemo vs osimertinib (see FDA approval)
mPFS: 25.5 vs 16.7 mo (HR, 0.62)
Erlotinib
EU RTAC: Erlotinib vs chemo
mPFS: 9.7 vs 5.2 mo (HR, 0.37)
Afatinib
LUX-Lung 3: Afatinib vs cis/pemetrexed
mPFS: 13.6 vs 6.9 mo (HR, 0.47)
Gefitinib
IFUM: Gefitinib single arm
mPFS: 9.7 mo
Dacomitinib
ARCHER 1050: Dacomitinib vs gefitinib
mOS: 34.1 vs 27 mo (HR, 0.75)
Erlotinib + ramucirumab
R E L AY: Erlotinib + ramucirumab vs erlotinib
mPFS: 19.4 vs 12.4 mo (HR, 0.59)
Erlotinib + bevacizumab (nonsquamous)
ARTEMIS-CTONG1509 : Erlotinib + bevacizumab vs erlotinib
mPFS: 17.9 vs 11.2 mo (HR, 0.55)
Amivantamab + lazertinib
MARIPOSA: Amivantamab + lazertinib vs osimertinib (see FDA approval)
PFS: 23.7 mo vs 16.6 mo
Amivantamab + carboplatin + pemetrexed (nonsquamous)
MARIPOSA-2: Amivantamb + chemo ± lazertinib vs chemo
mPFS: 6.3, 8.3 vs 4.2 mo (HR, 0.48, 0.44); ORR: 64%, 63% vs 36% (P < .001 for both)
MET (exon 14)
Capmatinib
a
GEOMETRY mono-1: Capmatinib single arm (see FDA approval)
mPFS: 12.4 mo; treatment-naïve patients, ORR: 68% (95% CI, 55 -80); DOR: 16.6 mo
Previously treated patients, ORR: 44% (95% CI, 34-54); DOR: 9.7 mo
Tepotinib
a
VISION: Tepotinib single arm
mPFS: 8.5 -11 mo
Crizotinib
PROFILE 1001: Crizotinib single arm
ORR: 32%
2L: HER2
Trastuzumab deruxtecan
a
DESTINY-Lung02: T-DXd 5.4 mg/kg vs 6.4 mg/kg (see FDA approval)
ORR: 58% (98% CI, 43-71); mDOR: 8.7 mo (95% CI, 7.1-NE)
Trastuzumab emtansine
NCT02675829: Trastuzumab emtansine single arm
ORR: 44%
T1-2, N2–3, M0
T3, N1–3, M0
T4, N0–3, M0
Tx
Nx
M1
Actionable mutation detected
Mutation (broad NGS if possible) and PD-L1 testing
NSCLC treatment algorithm
Stage and workup based on stage
• cT1abc, N0: PFT, bronch, mediastinal staging, PET
• cT2a- 4, N0-3, M0-1: PFT, bronch, mediastinal staging, PET, brain MRI, and biomarker/mutation testing
Please see the next page for recommendations if no actionable mutation is detected
Stage IV
• EGFR
• ALK
• ROS1
• BRAF V600E
• RET
• MET (ex14)
• HER2
• NTRK1/2/3
• KRAS G12C
NSCLC Treatment Algorithm
1

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3. a
Denotes NCCN-preferred regimens.
b
For patients who have no contraindications to PD-1 or PD-L1 inhibitors and who have a PS 0-1.
1. Adapted from an algorithm created by Aakash Desai, MBBS, MPH, and Matthew Ho, MD, PhD, with recent updates from NCCN Guidelines Version 8, 2024. Used with permission from the authors.
PD- L1 <1%
b
IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + paclitaxel/nab-paclitaxel)
KEYNOTE-407: Pembro + chemo vs chemo
mPFS: 6.4 vs 4.8 mo (HR, 0.56); mOS: 15.9 vs 11.3 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(paclitaxel + carboplatin/cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
NONSQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
KEYNOTE-189: Pembro + chemo vs chemo
mPFS: 8.8 vs 4.9 mo (HR, 0.52); 12-mo OS: 69% vs 49% (HR, 0.49)
• Atezolizumab + chemotherapy (carboplatin + paclitaxel + bevacizumab)
IMpower150: Atezo + chemo vs chemo
mPFS: 8.3 vs 6.8 mo (HR, 0.62)
• Atezolizumab + chemotherapy (carboplatin + nab-paclitaxel)
IMpower130: Atezo + chemo vs chemo
mOS: 18.6 vs 13.9 mo (HR, 0.79); mPFS: 7.0 vs 5.5 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
DUAL IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Nivolumab + ipilimumab + chemotherapy (paclitaxel/carboplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
mOS: 14.1 vs 10.7 mo
• Durvalumab + tremelimumab + chemotherapy (carboplatin + nab-paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
• Durvalumab + tremelimumab + chemotherapy (gemcitabine + carboplatin/cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
NONSQUAMOUS:
• Nivolumab + ipilimumab + chemotherapy (paclitaxel/carboplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
mOS: 14.1 vs 10.7 mo
• Durvalumab + tremelimumab + chemotherapy (carboplatin + nab - paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
• Durvalumab + tremelimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
DUAL IMMUNOTHERAPY
Nivolumab + ipilimumab
CheckMate -227: Nivo/ipi vs chemo
mOS: 17.1 vs 14.9 mo
DUAL IMMUNOTHERAPY
Nivolumab + ipilimumab
CheckMate -227: Nivo/ipi vs chemo
mOS: 17.1 vs 14.9 mo
DUAL IMMUNOTHERAPY + CHEMOTHERAPY
Nivolumab + ipilimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
mOS: 14.1 vs 10.7 mo
Durvalumab + tremelimumab + chemotherapy (carboplatin + nab-paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
Durvalumab + tremelimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
IMMUNOTHERAPY MONOTHERAPY
Pembrolizumab
KEYNOTE-042: Pembro vs plat-based chemo
mOS: 16.7 vs 12.1 mo (HR, 0.81)
DUAL IMMUNOTHERAPY
Nivolumab + ipilimumab
CheckMate -227: Nivo/ipi vs chemo
mOS: 17.1 vs 14.9 mo
DUAL IMMUNOTHERAPY + CHEMOTHERAPY
Nivolumab + ipilimumab + chemotherapy (pemetrexed + carboplatin/cisplatin)
CheckMate -9LA: Nivo/ipi + chemo vs chemo
OS: 14.1 vs 10.7 mo
Durvalumab + tremelimumab + chemotherapy (carboplatin + nab-paclitaxel)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
Durvalumab + tremelimumab + chemotherapy (pemetrexed + carboplatin/
cisplatin)
POSEIDON: Durva/treme + chemo vs chemo (see FDA approval)
mOS: 13.3 vs 11.7 mo (HR, 0.86)
PD- L1 1%- 49%
IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + paclitaxel/nab-paclitaxel)
KEYNOTE-407: Pembro + chemo vs chemo
mPFS: 6.4 vs 4.8 mo (HR, 0.56); mOS: 15.9 vs 11.3 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(paclitaxel + carboplatin/cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
NONSQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + pemetrexed)
KEYNOTE-189: Pembro + chemo vs chemo
mPFS: 8.8 vs 4.9 mo (HR, 0.52); 12-mo OS: 69% vs 49% (HR, 0.49)
• Atezolizumab + chemotherapy (carboplatin + paclitaxel + bevacizumab)
IMpower150: Atezo + chemo vs chemo
mPFS: 8.3 vs 6.8 mo (HR, 0.62)
• Atezolizumab + chemotherapy (carboplatin + albumin-bound paclitaxel)
IMpower130: Atezo + chemo vs chemo
mOS: 18.6 vs 13.9 mo (HR, 0.79); mPFS: 7.0 vs 5.5 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
PD-L1 ≥50%
IMMUNOTHERAPY MONOTHERAPY
Pembrolizumab
a
KEYNOTE-024: Pembro vs platinum-based chemo
mPFS: 10.3 vs 6 mo (HR, 0.50)
Atezolizumab
a
I M p ower 110: Atezo vs platinum-based chemo
mOS: 20.1 vs 13.1 mo (HR, 0.59)
Cemiplimab
a
EMPOWER-Lung1: Cemi vs platinum-based chemo
mPFS: 8.2 vs 5.7 mo; mOS: NR vs 14.2 mo (HR, 0.57)
IMMUNOTHERAPY + CHEMOTHERAPY
SQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin + paclitaxel/nab-paclitaxel)
KEYNOTE-407: Pembro + chemo vs chemo
mPFS: 6.4 vs 4.8 mo (HR, 0.56); mOS: 15.9 vs 11.3 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(paclitaxel + carboplatin/cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
NONSQUAMOUS:
• Pembrolizumab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
KEYNOTE-189: Pembro + chemo vs chemo
mPFS: 8.8 vs 4.9 mo (HR, 0.52); 12-mo OS: 69% vs 49% (HR, 0.49)
• Atezolizumab + chemotherapy (carboplatin + paclitaxel + bevacizumab)
IMpower150: Atezo + chemo vs chemo
mPFS: 8.3 vs 6.8 mo (HR, 0.62)
• Atezolizumab + chemotherapy (carboplatin + albumin-bound paclitaxel)
IMpower130: Atezo + chemo vs chemo
mOS: 18.6 vs 13.9 mo (HR, 0.79); mPFS: 7.0 vs 5.5 mo (HR, 0.64)
• Cemiplimab + chemotherapy
a
(carboplatin/cisplatin + pemetrexed)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
• Cemiplimab + chemotherapy (paclitaxel + carboplatin or cisplatin)
EMPOWER-Lung 3: Cemi + chemo vs chemo (see FDA approval)
mOS: 21.9 vs 13 mo (HR, 0.7)
No actionable mutation detected (stratify based on PD-L1 staining %)
NSCLC Treatment Algorithm
1

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4. Immune-Related Adverse Events of Cancer Immunotherapies
1-6

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Immune checkpoint inhibitors (ICIs)—which are monoclonal antibodies against
CTLA-4, PD-1, or PD-L1—have transformed treatment of many cancer types.
However, these treatments are associated with immune-related adverse events (irAEs).
Pre-existing autoimmune disease
is a strong risk factor for irAEs
Mechanism of irAEs
• CTLA-4 inhibitors: an imbalance in the ratio of regulatory T cells to type 17 T helper cells,
autoantibody production, and complement-mediated cellular damage
• PD-1/PD-L1 inhibitors: less well understood but could be due to reduced regulatory T cell numbers
Diagnostic
workup of
individuals
with suspected
irAEs depends
on the affected
organ
SYSTEMIC
Sicca syndr ome and v asculitis
irAEs can r ange
in severity and
affect almost
any or gan
Polyneur opathy
Uveitis
Interstitial
lung
disease
Hepatitis
Vitiligo
Myalgia
and
myositis
Enterocolitis
Thyroiditis
Hypophysiti s
Myocar ditis
Adrenitis
Arthralgia
and
arthritis
Monitoring organ function during ICI
therapy to enable early detection of
irAEs is warranted only for some
organs, such as thyroid and liver
Endocrinopathies: most common
toxicities associated with
PD-1/PD-L1 monotherapy
Most common fatal
toxicity associated with
PD-1/PD-L1/CTLA-4
combination therapy 
Pneumonitis: most
common fatal toxicity
associated with PD-1/
PD-L1 monotherapy 
Common toxicity
associated with
immunotherapy and targeted
therapy combinations 
Cutaneous toxicities
are the earliest toxicity
associated with PD-1/
PD-L1 monotherapy
and combinations
Nephritis
Common toxicity
associated
with chemo +
IO regimens
Patterns and Duration of Various irAEs
While onset of irAEs is generally 2 to 16 weeks after ICI initiation, some reports
have noted onset within a few days of starting therapy and >1 year after completion.
An irAE that occurs >3 months after ICI discontinuation is a delayed/late-onset irAE.
Some irAEs are recurrent (ie, occurring in the same organ or >1 time after
discontinuation), while others are chronic and can be active (ie, requiring
immunosuppression) or inactive (ie, not requiring immunosuppression).
468101214 >30
Duration of Treatment, wk
PD-1/PD-L1 Inhibitors
Toxicity Grade
468101214 >30
Duration of Treatment, wk
PD-1/PD-L1 + CTLA-4 Inhibitors
Toxicity Grade
468101214 >30
CTLA-4 Inhibitors
Duration of Treatment, wk
Toxicity Grade
Colitis
Liver toxicity
Skin toxicity,
rash, or pruritus
Pneumonitis
Endocrinopathy
Nephritis
Become Aware and Stay Vigilant

5. Immune-Related Adverse Events of Cancer Immunotherapies
1-6

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General Management Recommendations
Increasing intensity
of treatment required
Grade 2Grade 1 Grade 3 Grade 4
ModerateMild Severe Very severe
Symptomatic and suppor tive therapy
Stop treatment
Some irAEs are unresponsive or resistant to treatment with steroids, while others
are steroid-dependent, requiring chronic treatment (≥12 weeks)
Oral steroids Intravenous steroids. ------------ >
•Referral to specialist
•Strong immune suppressive treatment
Increasing grade of irAE
Intravenous steroids
Steroids (PO/IV): 1-2 mg/kg/day
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 endocrinopathies
once managed
Managed in outpatient/
communi ty setting
Generally requires
hospital admission

6. Immune-Related Adverse Events of Cancer Immunotherapies
1-6

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Diagnosis and Management of Pulmonary irAEs
 Hold immunotherapy and reassess in 1-2 weeks
 Pulse oximetry rest and ambulation
 Consider chest imaging with CT (with contrast preferred)
 Repeat in 3-4 weeks
Moderate (grade 2): 25%-50%
lung involved
Severe (grade 3-4)
Grade 3: all lobes of lung or
>50% of lung parenchyma;
limited ADLs, oxygen requirement
Grade 4: life-threatening
 Hold immunotherapy
 Infectious workup (nasal swab, sputum, blood)
 Consider bronchoscopy and BAL
 Chest imaging with CT contrast
 Repeat in 3-4 weeks
 Consider empiric antibiotics
 Refractory: methylprednisolone 1-2 mg/m
2
/day; if no response in 3-4 days, treat as grade 3
 Permanently discontinue immunotherapy and move to inpatient care
 Infectious workup (nasal swab, sputum, blood)
 Pulmonary and infectious disease consultation
 Bronchoscopy with BAL
 Empiric antibiotics
 Methylprednisolone 1-2 mg/m
2
/day; when grade 1, taper over 6 weeks
 Refractory: infliximab, mycophenolate, or IVIG
 Pneumonitis: focal or diffuse inflammation of the lung parenchyma (typically identified on CT imaging)
 Diagnostic workup: CXR, CT, pulse oximetry; for grade ≥2, may include infectious workup
Mild (grade 1): <25% lung
involved
Additional considerations
• GI and pneumocystis prophylaxis may be offered to patients on prolonged steroid use (>12 weeks)
• Consider calcium and vitamin D supplementation with prolonged steroid use
• Bronchoscopy and biopsy; if clinical picture is consistent with pneumonitis, no need for biopsy
Supportive care: smoking cessation and vaccinations (influenza, pneumococcal)

7. Immune-Related Adverse Events of Cancer Immunotherapies
1-6

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Guideline Management Recommendations
1. Ramos-Casals M et al. Nat Rev Dis Primers. 2020;6:38. 2. Martins F et al. Nat Rev Clin Oncol. 2019;16:563-580. 3. O’Leary CL et al. J Thorac Oncol. 2023;19:395-408. 4. Naidoo J et al. J Immunother Cancer. 2023;11:e006398. 5. Provided courtesy of Prof. Peter Schmidt, FRCP, MD, PhD.
6. Brahmer JR et al. J Clin Oncol. 2018;36:1714 -178 6 .