Sequential targeting in multiple myeloma: talquetamab, a GPRC5D bispecific antibody, as a bridge to BCMA CAR-T therapy
Abstract
Abstract Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), 2 B-cell maturation antigen (BCMA)–directed chimeric antigen receptor T-cell (CAR-T) therapies, have transformed outcomes for relapsed/refractory multiple myeloma; however, the 6 to 8 weeks manufacturing time risks disease progression or death in up to 10% of patients. Talquetamab, a G-protein–coupled receptor, family C, group 5, member D (GPRC5D)–targeting bispecific antibody, represents a promising option. We performed a multi-institutional retrospective analysis across 20 centers (18 United States, 2 Germany) evaluating talquetamab as a bridging therapy prior to cilta-cel or ide-cel. Among 134 patients receiving talquetamab, 119 proceeded to CAR-T (n = 98 cilta-cel, n = 21 ide-cel). Reasons for not proceeding (n = 15) included progression (n = 7), manufacturing failure (n = 6), or patient decision (n = 2). Median age was 65 years and had median 5 prior lines of therapy. Notably, 85% would not have met CARTITUDE-1/KarMMa eligibility criteria. Talquetamab was administered for a median 23 days. Toxicity was manageable: no grade ≥3 cytokine release syndrome (CRS), 2% grade 3 immune effector cell–associated neurotoxicity syndrome (ICANS) and grade 1 to 2 talquetamab unique toxicities (70% oral, 38% skin, and 17% nail; 60% resolved). Talquetamab achieved 71% response rate. After CAR-T, 88% responded (54% complete response), with low-grade toxicities (2 grade ≥3 CRS, 1 grade 3 ICANS, and 5% grade ≥3 infections). Two cases of facial palsy and 1 acute myeloid leukemia occurred. Talquetamab correlated with sustained soluble BCMA decline and peak CAR-T expansion around day 14. Talquetamab bridging appears safe, enabling the majority of difficult-to-treat patients to successfully proceed to BCMA CAR-T therapy.
Article Details
Authors (43)
Binod Dhakal
2Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
Othman S. Akhtar
4Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
David Fandrei
2Institut Gustave Roussy, Computational Clinical Oncology Lab, UMR 981, Villejuif, France
Alexandria Jensen
Rahul Banerjee
Darren Pan
1University of California San Francisco, San Francisco, United States
Shambavi Richard
Icahn School of Medicine at Mount Sinai, New York
Reed Friend
2Levine Cancer Institute, Atrium Health, Wake Forest University School of Medicine, charlotte, United States
Matthew Rees
1St. Jude Children's Research Hospital, Oncology, Memphis, United States
Patrick Costello
9Division of Hematology, Dana-Farber Cancer Institute, Boston, MA
Mariola Vazquez Martinez
10Division of Hematology and Cell Therapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Oren Pasvolsky
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Charlotte Wagner
James A. Davis
13Division of Hematology-Oncology, Medical University of South Carolina, Charleston, SC
Omar Castaneda Puglianini
10Division of Hematology and Cell Therapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Ran Reshef
13Division of Hematology/Oncology, Blood and Marrow Transplantation and Cell Therapy Program, Columbia University Irving Medical Center, New York, NY
Aimaz Afrough
Myeloma, Waldenstrom’s, and Amyloidosis Program, Hematologic Malignancies and Cellular Therapy Program, Simmons Comprehensive Cancer Center (A.A.), University of Texas Southwestern Medical Center, Dallas, TX.
Danai Dima
Fred Hutchinson Cancer Center, Seattle, Washington, United States
Manisha Bhutani
Atrium Health Levine Cancer Institute, Charlotte, North Carolina, United States
Omar Nadeem
Ricardo Parrondo
2Mayo Clinic, Jacksonville, United States
Ciara Freeman
10Division of Hematology and Cell Therapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Lekha Mikkilineni
Stanford University School of Medicine, Palo Alto, California, United States
Shahzad Raza
Taussig Cancer Institute, Cleveland Clinic, Cleveland
Larry D. Anderson Jr
15Division of Hematology, University of Texas Southwestern, Dallas, TX
Prashant Kapoor
Mayo Clinic, Rochester, MN
Hitomi Hosoya
Saurabh Chhabra
6The Mayo Clinic Arizona, Pheonix, United States
Ariel Grajales-Cruz
1H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States
Mahmoud Gaballa
4The University of Texas MD Anderson Cancer Center, Houston, United States
Shonali Midha
13Dana-Farber Cancer Institute, Boston, United States
Melissa Alsina
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States
Douglas Sborov
9University of Utah Huntsman Cancer Institute, Salt lake City, United States
Krina Patel
4The University of Texas MD Anderson Cancer Center, Houston, United States
Yi Lin
Christopher Ferreri
7Atrium Health Levine Cancer Institute, Charlotte, United States
Nico Gagelmann
From the Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anupama Kumar
1University of California San Francisco, San Francisco, United States
Doris Hansen
1H. Lee Moffitt Cancer Center and Research Institute, Tampa, United States
Andrew Cowan
3University of Washington and Fred Hutchinson Cancer Center, Seattle, United States
Luciano J. Costa
Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham
Maximilian Merz
11Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, NY
Surbhi Sidana
Stanford University School of Medicine, Palo Alto, CA