Restoring Remission in RRMM: Present and Future of Sequential Immunotherapy With GPRC5D-Targeting Options

Chair, Shaji K. Kumar, MD, prepared useful Practice Aids pertaining to multiple myeloma for this CME/NCPD/AAPA/IPCE activity titled “Restoring Remission in RRMM: Present and Future of Sequential Immunotherapy With GPRC5D-Targeting Options.” For the full presentation, downloadable Practice Aids, and complete CME/NCPD/AAPA/IPCE information, and to apply for credit, please visit us at https://bit.ly/4fYDKkj. CME/NCPD/AAPA/IPCE credit will be available until February 23, 2026.

1. NCCN Guideline Recommendations for Later-Line Use of
Bispecific Antibodies and Other Immunotherapy Options in RRMM

Full abbreviations, accreditation, and disclosure information available at PeerView.com/ESB40 For early relapse, the NCCN recommends the use of BCMA CAR-T
therapy and other SOC options depending on prior therapy
1
Preferred Regimens
• Anti-CD38 refractory: KRd, KPd, PVd, EloPd, and IxaPd
• Bortezomib refractory: KRd, KPd, Elo-Pd, and a variety of triplets with daratumumab
or isatuximab
• Lenalidomide refractory: KPd, Elo-Pd, IxaPd, PVd, and a variety of triplets with
daratumumab or isatuximab
CAR-T cell therapy
• Ciltacabtagene autoleucel (category 1)
– After 1 prior therapy including an IMiD, a PI, and refractory to lenalidomide
• Idecabtagene vicleucel (category 1)
– After 2 prior therapies including an IMiD, a PI, and an anti-CD38
monoclonal antibody
Therapies for Previously Treated RRMM After 1-3 Prior Therapies

2. NCCN Guideline Recommendations for Later-Line Use of
Bispecific Antibodies and Other Immunotherapy Options in RRMM

Full abbreviations, accreditation, and disclosure information available at PeerView.com/ESB40 For late relapse, the NCCN guidelines recommend the use of
BCMA CAR-T therapy and bispecific antibodies
1
Preferred Regimens
CAR-T cell therapy
• Ciltacabtagene autoleucel
• Idecabtagene vicleucel
Bispecific antibodies
After at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a PI, and
an IMiD
• Elranatamab-bcmm
• Talquetamab-tgvs
• Teclistamab-cqyv
Therapies for Late Relapse RRMM After >3 Prior Therapies
1. NCCN Clinical Practice Guidelines in Oncology. Multiple Myeloma. Version 1.2025. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf.

3. Resources for GPRC5D-Directed Therapy:
Dosing and Safety Considerations
1-4
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ESB40 Talquetamab
Indicated for the treatment of adult patients with RRMM who have received at least
4 prior therapies, including an anti-CD38 monoclonal antibody, a PI, and an IMiD
Patients should be hospitalized for 48 hours after all doses within the step-up dosing schedule
Additional dosing principles for talquetamab
a
Based on actual body weight.
b
Dose may be administered between 2-4 days after the previous dose and may be given up to 7 days after the previous dose to allow for
resolution of adverse reactions.
c
Dose may be administered between 2-7 days after step-up dose 3.
d
Maintain a minimum of 12 days between Q2W doses.
Step-up dose 1:
0.01 mg/kg
Step-up dose 2:
0.06 mg/kg
Treatment dose 1:
0.4 mg/kg
Step-up dose 3:
0.4 mg/kg
Treatment dose 1:
0.8 mg/kg
Subsequent treatment doses:
0.8 mg/kg Q2W
d
Subsequent treatment doses: 0.4 mg/kg QW
Day 10
c
Day 7
b
Day 4
b
Day 1
0.4 mg/kg QW
0.8 mg/kg Q2W
2 weeks after first dose
1 week after first dose
Dosing
a
and Administration Principles

4. Resources for GPRC5D-Directed Therapy:
Dosing and Safety Considerations
1-4
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ESB40 • Monitor vitals every 4 hours per
institutional guidelines
• Watch closely for signs and
symptoms of CRS
• Monitor for signs of
neurotoxicity and consider
neurology evaluation at first
sign of confusion
or disorientation
• Instruct patients to report any
changes to taste or skin/nails
Post-injection
• Monitor patients for weight
loss; consider nutritionist
consultation
• Evaluate doses of weight-
based medications if
significant weight loss occurs
• Evaluate dermatologic/oral AEs
• Discuss supportive measures
for dermatologic/oral AEs
• Monitor for secondary
skin infection
Subsequent visits
• Evaluate patient for signs of
infection or symptoms of
unresolved CRS/ICANS from
previous dose
• Administer premedications
1-3 hours before
talquetamab dose
• Ensure correct drug and
dosage are prepared
Pre-injection
General Monitoring Principles With Talquetamab

5. Resources for GPRC5D-Directed Therapy:
Dosing and Safety Considerations
1-4
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ESB40 • Baking soda/salt water/magic mouth rinse
• Alternative sources of protein if adverse to meat
• Add flavor with citrus, herbs, spices, and wine-based marinades
Dysgeusia
• Gum or hard candy, frozen fruit, ice chips, and
tart drinks
• Monitor for oral candidiasis
• Recommend routine dental exams
• Hydration
• Soft/bland foods, cold or room temperature
• Moisten food with broth or sauces
• Limit caffeine and alcohol intake
Dry mouth
• Soft or mashed foods
• Food purees
• Small bites
• Frequent small meals
• Avoid meat and dry foods, take sips of liquid
between bites
Dysphagia
• Small frequent meals and snacks with protein
• Nutrient-dense foods
• Add calorie-boosting foods (eg, olive oil, nut butter)
• Oral appetite stimulants
Weight loss
• Soaps for sensitive skin
• Colloidal oatmeal baths
• Can be escalated to triamcinolone cream or
methylprednisolone
• Hydration
• Emollients
• Lukewarm or cold showers
• Ammonium lactate for pruritus
• Oral antihistamines or topical steroids
Skin toxicity
• Vitamin E oil
• Biotin supplement
• Monitor for secondary nail infections
• Nail/finger cots or gloves
• File nails to smooth edges and corners
• Frequent applications of emollients
• Nail hardeners
Nail toxicities
Recommendations for Managing Specific Toxicities Associated With Talquetamab in RRMM

6. Grade 4Grade 3Grade 2Grade 1Parameter for CRS
Temp ≥38° C
(100.4° F)
Temp ≥38° C
(100.4° F)
Temp ≥38° C
(100.4° F)
Temp ≥38° C
(100.4° F)
Fever
With
Requiring multiple
vasopressors
(excluding vasopressin)
Vasopressor ± vasopressin requiredNo vasopressors requiredNoneHypotension
And/or
Positive pressure (eg,
CPAP, BiPAP, intubation,
and mechanical
ventilation) required
High-flow nasal cannula, facemask,
nonrebreather mask, or
Venturi mask required
Low-flow nasal cannula or
blow-by required
NoneHypoxia
To Address CRS With Immunotherapy
• Use tocilizumab
• If no improvement,
administer
methylprednisolone or
dexamethasone; if no
improvement, consider
alternative
immunosuppressants
• Use tocilizumab
• If no improvement, administer
methylprednisolone or
dexamethasone
• Use tocilizumab
• Use steroids per guidelines
if no improvement on
tocilizumab within 24 h
• Tocilizumab may be considered
• Steroids are not applicable
Nuances to Address CRS When Using Talquetamab
• Permanently discontinue
talquetamab +
supportive care
• For <48 h, withhold talquetamab
until CRS resolves +
supportive therapy
• Premedication prior to next dose
• 48 h hospitalization following next dose
• Recurrent or duration >48 h,
permanently discontinue
talquetamab + supportive care
• Withhold talquetamab until
CRS resolves
• Premedication prior to
next dose
• 48 h hospitalization following
next dose
• Withhold talquetamab until
CRS resolves
• Premedication prior to next dose
CRS Management Recommendations With Tocilizumab and Steroids
1. TALVEY (talquetamab) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761342s000lbl.pdf. 2. Lee D et al. Biol Blood Marrow Transplant. 2019;25:625-638. 3. Catamero D et al. Semin Onocol Nurs. 2024;40:151712.
4. Crombie J et al. Blood. 2024;143:1565 -1575.
Resources for GPRC5D-Directed Therapy:
General Recommendations for Cytokine Release Syndrome (CRS)
Management With Immunotherapy and Nuances With GPRC5D Therapy
1-4

Full abbreviations, accreditation, and disclosure information available at PeerView.com/ESB40

7. DOB:Patient name:
Current treatment:Diagnosis:
My highest risk of side effects is on (date): Treatment start date:
Treatment team:
Contact information:
Neurotoxicity symptoms to monitor for
• Confusion
• Difficulty with speech
• Difficulty staying awake
• Abnormal actions
• Seizures
CRS symptoms to monitor for
• Temperature 100.4° F or greater
• Pulse oxygen ≤90% or >5% change from baseline
• Decrease in SBP >10 mmHg from baseline and/or
SBP <90 mmHg
• Increased heart rate >110 or >20 bpm from baseline
while at rest
How often do I monitor?
What number should I call?
• During office hours:
• After office hours:
What do I monitor at home?
• Temperature
• Blood pressure
• Heart rate
• Oxygen levels
When do I call my doctor’s office?
• Any symptom of CRS or change in thinking or speech
When should I go straight to the ER?
Patient Information Sheet for TEAEs With Bispecifics in MM

8. Resources for Encouraging Patient Engagement in Care
From HealthTree Foundation for Multiple Myeloma
Full abbreviations, accreditation, and disclosure information available at PeerView.com/ESB40 HealthTree Foundation for Multiple Myeloma offers a wide range of resources that can be used to
encourage patients to learn more about their disease or a planned course of treatment
Patient education and navigation tools
Programs that create patient
connections and build community
A living, real-world evidence data
portal that delivers researchers the
data they need to accelerate a cure
Scan to visit:
healthtree.org/myeloma
Scan to visit:
youtube.com/watch?v=G7dfE0LcD2o
HealthTree Cure Hub: Connecting Patient
Data to Researchers to Accelerate Cures
Help patients get answers
to basic questions about myeloma
Scan to visit:
healthtree.org/myeloma/university
Selected Resources