Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-cell Therapy bb21217 for Relapsed and Refractory Multiple Myeloma: Results from the Phase I CRB-402 Study

Chimeric antigen receptor (CAR) T-cell therapy enriched for a memory-like phenotype may persist and function longer than a non-enriched product, thereby improving duration of response (DOR). We conducted a phase 1 study with bb21217 (NCT03274219), an anti-B-cell maturation antigen CAR T-cell therapy manufactured in the presence of bb007 (phosphoinositide 3-kinase inhibitor) to enrich for T cells with a memory-like phenotype, in patients with relapsed/refractory multiple myeloma (N=72). No new safety concerns were raised with bb21217 therapy (three cases each of grade ≥3 CRS and grade ≥3 neurotoxicity were observed). The objective response rate was 69.4% and median DOR was 23.8 (95% confidence interval, 16.8-34.8) months. Analysis of drug product established an association between early memory phenotype and robust expansion and depth of response. Examination of baseline characteristics indicated that tumor burden and prior therapies influenced DOR. The generation of CAR T cells early in a disease course when tumor burden is lower and source material exhibits a more naïve phenotype may maximize the clinical benefit potential of the drug product.

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Publication Details

Journal
Cancer Immunology Research
Published
2026-01-21
DOI
https://doi.org/10.1158/2326-6066.cir-24-0527
Primary Topic
CAR-T cell therapy research
Type
article
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article

Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-cell Therapy bb21217 for Relapsed and Refractory Multiple Myeloma: Results from the Phase I CRB-402 Study

Timothy Campbell, Pingping Mao, Y Lin, Sundar Jagannath et al.
Cancer Immunology Research
CAR-T cell therapy research
article

Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-cell Therapy bb21217 for Relapsed and Refractory Multiple Myeloma: Results from the Phase I CRB-402 Study

Timothy Campbell, Pingping Mao, Y Lin, Sundar Jagannath, Anna Truppel-Hartmann, Jesús G. Berdeja, Raje NS, Jacalyn Rosenblatt, Benjamin Avi Derman, Melissa Alsina, Fabio Petrocca, Olivia Finney, Nathan Martin, Andrzej J. Jakubowiak, Jonathan L. Kaufman, David Siegel, Maeva Fincker, Aojun Li, Nikhil C. Munshi, Nina Shah
article en

Abstract

Chimeric antigen receptor (CAR) T-cell therapy enriched for a memory-like phenotype may persist and function longer than a non-enriched product, thereby improving duration of response (DOR). We conducted a phase 1 study with bb21217 (NCT03274219), an anti-B-cell maturation antigen CAR T-cell therapy manufactured in the presence of bb007 (phosphoinositide 3-kinase inhibitor) to enrich for T cells with a memory-like phenotype, in patients with relapsed/refractory multiple myeloma (N=72). No new safety concerns were raised with bb21217 therapy (three cases each of grade ≥3 CRS and grade ≥3 neurotoxicity were observed). The objective response rate was 69.4% and median DOR was 23.8 (95% confidence interval, 16.8-34.8) months. Analysis of drug product established an association between early memory phenotype and robust expansion and depth of response. Examination of baseline characteristics indicated that tumor burden and prior therapies influenced DOR. The generation of CAR T cells early in a disease course when tumor burden is lower and source material exhibits a more naïve phenotype may maximize the clinical benefit potential of the drug product.

Cancer Immunology Research
Beth Israel Deaconess Medical Center (US), Hackensack University Medical Center (US), Mayo Clinic (US), Emory University (US), University of California, San Francisco (US), Moffitt Cancer Center (US), University of Illinois Chicago (US), University of Chicago (US), Massachusetts General Hospital (US), Mount Sinai Medical Center (US), Dana-Farber Cancer Institute (US), Mayo Clinic in Arizona (US), Tisch Hospital (US), Bristol-Myers Squibb (Sweden) (SE), Tennessee Oncology (US), Mayo Clinic in Florida (US), Center for Cancer Research (US)
Good health and well-being
Openalex Percentile: Top 82%
CAR-T cell therapy research
DOISourceOpenAlex
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