Advances in CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma: A Systematic Review and Meta-Analysis of Clinical Trials in the Last Two Years

Author Type(s)

Faculty, Resident/Fellow

Document Type

Abstract

Publication Date

9-2023

DOI

10.1016/S2152-2650(23)01427-1

Journal Title

Clinical Lymphoma Myeloma & Leukemia

Department

Medicine

Abstract

Background

T-cells are engineered to express chimeric antigen receptors (CAR) to target cancer-associated antigens. In this systematic review and meta-analysis, we will assess the efficacy of CAR-T cell therapies in relapsed/refractory multiple myeloma (RRMM) tested in the last 2 years.

Methods

A literature search was performed on PubMed, Embase, and clinicaltrials.gov with the keywords “multiple myeloma” and “CAR-T cell therapy” from 1/1/2021 to 2/31/2023. We screened 1,818 articles and included the results of 15 clinical trials (N=660). We used R software to conduct this meta-analysis.

Results

Among 660 patients in 15 clinical trials, 573 patients were treated with autologous anti-B-cell maturation antigen (anti-BCMA), 21 patients were treated with allogenic anti-BCMA, 25 patients were treated with anti-GPRC5D, and 41 patients were treated with dual target CAR-T cell agents. In 10 clinical trials (N=573) on anti-BCMA CAR T-cell therapy, pooled overall response (ORR), pooled complete response (CR), and pooled negative minimal residual disease (-MRD) were 90% (CI=80%-95%, I2=83%), 47% (CI=36%-58%, I2=84%), and 37% (CI=26%-50%, I2=85%), respectively. In two clinical trials (N=25) on anti-GPRC5D CAR T-cell therapy in patients pretreated with anti-BCMA, ORR, CR, -MRD, were 80% (CI=43%-96%, I2=37%), 36% (CI=20%-56%, I2=0), and 28% (CI=14%-49%, I2=0), respectively. In a clinical trial (N=21) on anti-BCMA allogenic CAR T-cell therapy, ORR, CR, -MRD were 71% (CI=48%-89%, I2=0%), 24% (CI=20%-47%, I2=0), and 24% (CI=8%-47%, I2=0), respectively. In two clinical trials (N=41) on dual-target CAR T-cell therapy, ORR, CR, -MRD was 84% (CI=69%-93%, I2=4%), 75% (CI=55%-89%, I2=0), and 75% (CI=55%-89%, I2=0), respectively.

Conclusion

Anti-BCMA, anti-GPRC5D, allogenic anti-BCMA, and dual-target CAR T-cell were effective in heavily pretreated MM patients. Anti-GPRC5D showed a response in BCMA-pretreated patients. Response rates were similar among anti-BCMA, anti-GPRC5D, allogenic anti-BCMA, and dual-target CAR T-cell therapies. More randomized trials are needed to confirm these results.

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