Sequencing BCMA-Directed Therapies in Relapsed/Refractory Multiple Myeloma: A Real-World Comparison of CAR T-Cell Therapy and Bispecific Antibodies.
10 affiliations
- 1School of Medicine, University of Jordan, Amman 11942, Jordan.
- 2Division of Hematology and Oncology, University of Cincinnati, Cincinnati, OH 45267, USA.
- 3St. John's Episcopal Hospital, New York, NY 11691, USA.
- 4Levine Cancer Center, Atrium Health, Wake Forest University School of Medicine, Charlotte, NC 28204, USA.
- 5Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA 52242, USA.
- 6Division of Hematology and Oncology, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36688, USA.
- 7Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA.
- 8Division of Blood Disorders, Rutgers Cancer Institute, New Brunswick, NJ 08901, USA.
- 9Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS 66160, USA.
- 10Division of Hematology, The Ohio State University, Columbus, OH 43210, USA.
Abstract
Background
Several B-cell maturation antigen (BCMA)-directed therapy (BDT) modalities have been approved by the US Food and Drug Administration (FDA) for relapsed-refractory multiple myeloma (RRMM). Ideal sequencing of these therapies remains unknown.Methods
We report one of the largest multicenter retrospective patient cohorts in this real-world analysis of patients receiving a BDT in both BDT-naïve and exposed settings at major academic centers.Results
In the BDT-naïve setting, which included 276 patients, 169 (61%) received chimeric antigen receptor T-cell therapy (CAR-T), whereas 107 (39%) received bispecific antibodies (BsAbs). Median progression-free survival (PFS) in the BDT-naïve setting was significantly longer with CAR-T than with BsAbs (16.1 vs. 13.5 months, p = 0.007) with a higher overall response rate (ORR) (87 vs. 68%). Multivariable Cox regression analysis revealed that receiving CAR-T (hazard ratio [HR] = 0.41), cytokine release syndrome (CRS) of any grade (HR = 0.50), achieving a best response of ≥very good partial response (VGPR) (HR = 0.12), and high-risk cytogenetic abnormalities (HRCA) (HR = 2.29) were all significant prognostic indicators of PFS. Similarly, HRCA (HR = 2.32), CRS (HR = 0.36), and a best response of ≥VGPR (HR = 0.16) were all independent prognostic factors of overall survival (OS). Of the 80 patients who received prior BDT, 22 received CAR-T (28%) and 58 (72%) received BsAbs. The median PFS was 6.3 months in the CAR-T group, with 64% ORR, vs. 4.4 months in the BsAb group, with 53% ORR (PFS HR, 0.93). Only the best response, ≥VGPR (HR = 0.20), achieved significance in the multivariable model.Conclusions
CAR-T led to more durable responses in the BDT-naïve setting than BsAbs. Responses to either modality were weaker in the BDT-exposed setting. These results highlight the importance of sequencing BDT in RRMM.
Related
- HIGH INFECTION BURDEN IN MULTIPLE MYELOMA TREATED WITH CONVENTIONAL THERAPIES AND BISPECIFIC ANTIBODIES: REAL-WORLD DATA
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- BISPECIFIC ANTIBODIES IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS OF EFFICACY AND SAFETY
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BibTeX
@article{younis2026sequencing,
title = {{Sequencing BCMA-Directed Therapies in Relapsed/Refractory Multiple Myeloma: A Real-World Comparison of CAR T-Cell Therapy and Bispecific Antibodies.}},
author = {Osama M Younis and Sencer Goklemez and Carmel Awadallah and Shebli Atrash and Barry Paul and Hira Shaikh and Christopher Strouse and Andrew Vegel and Emily Struble and Anita Mazloom and Omar Alkharabsheh and Prerna Mewawalla and Mansi R Shah and Abhiraj Saxena and Zahra Mahmoudjafari and Jordan Snyder and Muhammad Umair Mushtaq and Jeries Kort and Alma Habib and Joseph McGuirk and Al-Ola Abdallah and Abdullah Mohammad Khan},
journal = {Cancers},
year = {2026},
month = sep,
doi = {10.3390/cancers18193147},
url = {https://europepmc.org/article/MED/42882842},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sequencing BCMA-Directed Therapies in Relapsed/Refractory Multiple Myeloma: A Real-World Comparison of CAR T-Cell Therapy and Bispecific Antibodies.
AU - Osama M Younis
AU - Sencer Goklemez
AU - Carmel Awadallah
AU - Shebli Atrash
AU - Barry Paul
AU - Hira Shaikh
AU - Christopher Strouse
AU - Andrew Vegel
AU - Emily Struble
AU - Anita Mazloom
AU - Omar Alkharabsheh
AU - Prerna Mewawalla
AU - Mansi R Shah
AU - Abhiraj Saxena
AU - Zahra Mahmoudjafari
AU - Jordan Snyder
AU - Muhammad Umair Mushtaq
AU - Jeries Kort
AU - Alma Habib
AU - Joseph McGuirk
AU - Al-Ola Abdallah
AU - Abdullah Mohammad Khan
PY - 2026
DA - 2026/09/29
JO - Cancers
DO - 10.3390/cancers18193147
UR - https://europepmc.org/article/MED/42882842
AB - Background Several B-cell maturation antigen (BCMA)-directed therapy (BDT) modalities have been approved by the US Food and Drug Administration (FDA) for relapsed-refractory multiple myeloma (RRMM). Ideal sequencing of these therapies remains unknown.Methods We report one of the largest multicenter retrospective patient cohorts in this real-world analysis of patients receiving a BDT in both BDT-naïve and exposed settings at major academic centers.Results In the BDT-naïve setting, which included 276 patients, 169 (61%) received chimeric antigen receptor T-cell therapy (CAR-T), whereas 107 (39%) received bispecific antibodies (BsAbs). Median progression-free survival (PFS) in the BDT-naïve setting was significantly longer with CAR-T than with BsAbs (16.1 vs. 13.5 months, p = 0.007) with a higher overall response rate (ORR) (87 vs. 68%). Multivariable Cox regression analysis revealed that receiving CAR-T (hazard ratio [HR] = 0.41), cytokine release syndrome (CRS) of any grade (HR = 0.50), achieving a best response of ≥very good partial response (VGPR) (HR = 0.12), and high-risk cytogenetic abnormalities (HRCA) (HR = 2.29) were all significant prognostic indicators of PFS. Similarly, HRCA (HR = 2.32), CRS (HR = 0.36), and a best response of ≥VGPR (HR = 0.16) were all independent prognostic factors of overall survival (OS). Of the 80 patients who received prior BDT, 22 received CAR-T (28%) and 58 (72%) received BsAbs. The median PFS was 6.3 months in the CAR-T group, with 64% ORR, vs. 4.4 months in the BsAb group, with 53% ORR (PFS HR, 0.93). Only the best response, ≥VGPR (HR = 0.20), achieved significance in the multivariable model.Conclusions CAR-T led to more durable responses in the BDT-naïve setting than BsAbs. Responses to either modality were weaker in the BDT-exposed setting. These results highlight the importance of sequencing BDT in RRMM.
SN - 2072-6694
ER -