Chimeric Antigen Receptor T Cells (CAR-T) Vs. Bispecific Antibody (BsAb) Against B-Cell Maturation Antigen (BCMA) in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM): A Systematic Review and Metaanalysis

Introduction:

CAR-T cell and BsAb targeting BCMA have shown significant efficacy in patients (pts) with RRMM. To date, two BCMA targeting CAR-T and two BsAb therapies have been approved for RRMM. CAR-T is a one-time treatment with complex logistics, while BsAb is an “off-the-shelf” therapy requiring continuous treatment. Both treatments exhibit unique adverse events (AEs). This systematic review and meta-analysis compare the efficacy and safety of these two therapies.

Methods:

We searched MEDLINE, Scopus, Cochrane databases, and conference abstracts from ASCO, ASH, and EHA until June 2024 for trials evaluating BCMA CAR-T and BsAb in patients with three or more prior line of therapy (LOT). The primary endpoints were overall response rate (ORR) and complete response (CR) rates. Safety endpoints included all grade AEs, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), infections, cytopenias, and non-relapse mortality (NRM). NRM was defined as death in the absence of recurrent or progressive myeloma. Individual study event probabilities were reported with exact binomial (Clopper-Pearson) confidence intervals. Random intercept logistic regression models were used to combine estimates across studies, as well as to estimate the effect of treatment. Publication bias was assessed via funnel plots and Egger's test. Analyses were performed using R version 4.3.1.

Results:

A total of 25 studies (18 CAR-T, 7 BsAb) involving 1660 pts were included, with a median sample size of 43 (range 6-165). The median age was 63 yrs. (range 53-73) and 55% were male. The median prior LOT was five (range 3-9). The pooled ORR was

significantly higher for CAR-T (92%) compared to BsAb (60%) (OR 5.98, 95% CI 2.31-15.5, p<0.001). CAR-T also had higher CR and better rates (57% vs. 32%; OR 2.96, 95% CI 1.51-5.8, p=0.002). In terms of safety, CAR-T was associated with more grade 3 or higher AEs (99% vs. 81%; OR 11.7, 95% CI 3.84-35.7; p<0.001), grade 3 or higher CRS (6% vs. 1%; OR 13.1, 95% CI 4.13-41.6, p<0.001), and grade 3 or higher ICANS (2% vs. 1%; OR 4.05, 95% CI 1.16-14.2, p=0.029). Cytopenia rates (all grades) were also higher with CAR-T (91% vs. 35%; OR 12.4, 95% CI 1.16-134, p=0.037). However, CAR-T had significantly lower infection rates (49% vs. 66%; OR 0.52, 95% CI 0.30-0.91, p=0.023). Despite higher grade 3 or higher AEs, CAR-T had comparable NRM (5% vs. 10%; OR 0.47, 95% CI 0.21-1.06, p=0.07).

Conclusions:

In pts with three or more prior LOT, BCMA CAR-T therapies yield higher and deeper response rates compared to BsAb in RRMM. CAR-T is associated with higher rates of severe AEs, CRS, and ICANS, but lower infection rates. The differences in the NRM likely reflect the differences in AE profiles. These findings provide valuable insights for treatment decisions and sequencing of these therapies in RRMM pts.

Mohan:Legend biotech: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy; Janssen: Consultancy. D'Souza:Abbvie: Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Prothena: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Research Funding; Takeda: Research Funding. Pasquini:Janssen: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding. Dhakal:Carsgen: Research Funding; Sanofi: Research Funding; Medical College of Wisconsin: Current Employment; C4 therapeutics: Research Funding; Karyopharm: Honoraria, Speakers Bureau; Genentech: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Acrellx: Research Funding; Bristol Myers Squibb: Honoraria, Research Funding.