Clinical Management of Patients With Relapsed/Refractory Multiple Myeloma Treated With Talquetamab.

Bispecific antibody Dermatologic toxicities GPRC5D Infections Oral events

Journal

Clinical lymphoma, myeloma & leukemia
ISSN: 2152-2669
Titre abrégé: Clin Lymphoma Myeloma Leuk
Pays: United States
ID NLM: 101525386

Informations de publication

Date de publication:
15 May 2024
Historique:
received: 11 03 2024
revised: 26 04 2024
accepted: 01 05 2024
medline: 14 6 2024
pubmed: 14 6 2024
entrez: 13 6 2024
Statut: aheadofprint

Résumé

Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552), overall responses rates were > 71% in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Due to the distribution of the target antigen, a unique pattern of GPRC5D-associated adverse events (AEs) was observed, together with T-cell redirection-associated AEs. Management strategies for talquetamab-associated AEs are described. GPRC5D-associated AEs included dermatologic (rash, nonrash, and nail toxicities) and oral AEs (dysgeusia, dysphagia, and dry mouth). The incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were consistent with other T-cell redirection therapies. The incidence of high-grade infections was lower than observed with B-cell maturation antigen-targeting bispecific antibodies, with less frequent use of intravenous immunoglobulin required. GPRC5D-associated AEs were mostly low grade and led to few discontinuations. Skin toxicities were managed with emollients, topical corticosteroids, and oral corticosteroids (for high-grade, persistent, or AEs that progress). Nail toxicities were commonly managed with emollients. Based on investigator experience, dose modification may be effective for controlling oral events. Observation for potential weight changes is required. Infections were managed per standard of care. CRS and ICANS were effectively managed, consistent with other trials of T-cell redirection therapies. Although talquetamab had a distinct safety profile, AEs were considered clinically manageable and mostly low grade. With appropriate education and support, health care practitioners can ensure patients with RRMM maintain quality of life and treatment adherence.

Sections du résumé

BACKGROUND BACKGROUND
Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552), overall responses rates were > 71% in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Due to the distribution of the target antigen, a unique pattern of GPRC5D-associated adverse events (AEs) was observed, together with T-cell redirection-associated AEs. Management strategies for talquetamab-associated AEs are described.
DISCUSSION CONCLUSIONS
GPRC5D-associated AEs included dermatologic (rash, nonrash, and nail toxicities) and oral AEs (dysgeusia, dysphagia, and dry mouth). The incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were consistent with other T-cell redirection therapies. The incidence of high-grade infections was lower than observed with B-cell maturation antigen-targeting bispecific antibodies, with less frequent use of intravenous immunoglobulin required. GPRC5D-associated AEs were mostly low grade and led to few discontinuations. Skin toxicities were managed with emollients, topical corticosteroids, and oral corticosteroids (for high-grade, persistent, or AEs that progress). Nail toxicities were commonly managed with emollients. Based on investigator experience, dose modification may be effective for controlling oral events. Observation for potential weight changes is required. Infections were managed per standard of care. CRS and ICANS were effectively managed, consistent with other trials of T-cell redirection therapies.
CONCLUSION CONCLUSIONS
Although talquetamab had a distinct safety profile, AEs were considered clinically manageable and mostly low grade. With appropriate education and support, health care practitioners can ensure patients with RRMM maintain quality of life and treatment adherence.

Identifiants

pubmed: 38871558
pii: S2152-2650(24)00174-5
doi: 10.1016/j.clml.2024.05.003
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Ajai Chari (A)

Department of Medicine, Hematology, and Medical Oncology and Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY. Electronic address: ajai.chari@ucsf.edu.

Amrita Krishnan (A)

Judy and Bernard Briskin Myeloma Center, City of Hope Comprehensive Cancer Center, Duarte, CA.

Leo Rasche (L)

Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.

Jing Christine Ye (JC)

Department of Lymphoma - Myeloma, Division of Cancer Medicine, MD Anderson Cancer Center, University of Texas, Houston, TX.

Alfred Garfall (A)

Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.

Rakesh Popat (R)

Hematology Department, University College London Hospitals NHS Foundation Trust, London, UK.

Brea Lipe (B)

Department of Medicine, University of Rochester Medical Center, Rochester, NY.

Xiang Qin (X)

Janssen Research and Development, Spring House, PA.

Michela Campagna (M)

Janssen Research and Development, Madrid, Spain.

Tara Masterson (T)

Janssen Research and Development, Spring House, PA.

Chalmer Tomlinson (C)

Janssen Research and Development, Raritan, NJ.

Brandi Hilder (B)

Janssen Research and Development, Spring House, PA.

Jaszianne Tolbert (J)

Janssen Research and Development, Spring House, PA.

Thomas Renaud (T)

Janssen Research and Development, Raritan, NJ.

M Damiette Smit (MD)

Janssen Biologics B.V., Leiden, The Netherlands.

Kathleen Gray (K)

Janssen Scientific Affairs, Horsham, PA.

Colleen Kane (C)

Janssen Research and Development, Spring House, PA.

Christoph Heuck (C)

Janssen Research and Development, Spring House, PA.

Niels W C J van de Donk (NWCJ)

Department of Hematology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Classifications MeSH