CAR T Reduces All-Cause Mortality Greater Than a Bispecific Antibody in MM

Treatment options for patients with multiple myeloma have increased in recent years, especially with the additions of 2 chimeric antigen receptor (CAR) T-cell therapies, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), and the bispecific antibody teclistamab.

Junmin Song, MD

Junmin Song, MD, resident physician in internal medicine, Jacobi Medical Center, Albert Einstein College of Medicine, compared these emerging B-cell maturation antigen (BCMA) treatments during a presentation at the ESMO Congress 2024, held September 13-16 in Barcelona, Spain.¹

With newer treatments being used to treat multiple myeloma, Song and colleagues compare these emerging B-cell maturation antigen (BCMA) treatments. However, with no head-to-head trials comparing efficacies and side effects, Song and his colleagues used real-world data to compare survival between the CAR T-cell therapies and bispecifics.

They found patients had improved overall survival on the CAR Ts over patients only receiving bispecifics. The study specifically covered a time period in which all 3 treatments were only available for treatment after 4 prior lines of therapy.^2-4 However, ide-cel and cilta-cel both received expanded approvals in 2024, which moved their use up to second-line therapy.^5,6

The researchers used the TriNetX US Collaborative Network database, a deidentified stratified electronic health record of more than 100 million patients from more than 60 health care organizations in the US. The study included 391 patients receiving CAR T-cell therapy (ide-cel = 277; cilta-cel = 114) and 458 receiving teclistamab. The mean age was 66 years and 54% were male. After 1:1 propensity score matching with teclistamab there were 2 comparison groups: ide-cel (n = 180) vs teclistamab (n = 180) and cilta-cel (n = 93) vs teclistamab (n = 93).

The mortality rate after up to 1 year of follow-up was lower for the CAR T cohort (20%) compared with teclistamab (30%) and the CAR T cohort also had significantly lower all-cause mortality at 3, 6, and 12 months of follow-up. At 12 months the HR was 0.62 (95% CI, 0.38-0.99).

The CAR T cohort had a higher risk of cytokine release syndrome (CRS) compared with the teclistamab group (50% vs 40%), Song noted. CRS mostly happened within the first month of therapy initiation. For neurotoxicity, there were no significant differences between the 2 therapies, with approximately 20% in both cohorts. For both cohorts, neurotoxicity also mostly happened within the first month of drug initiation.

Patients who were older (≥ 70 years) and those who did not undergo bone marrow transplantation benefitted more from CAR T-cell therapy with a better overall survival.

During the presentation, Song noted some limitations of the study, including that the study did not identify newly diagnosed vs relapsed disease, nor did it stratify standard vs high-risk multiple myeloma. Since the study was based on International Classification of Diseases, Tenth Revision, and the TriNetX codes, there may be miscoding.

“Based on our study, we hypothesize that upfront BCMA CAR T therapy in older transplant-ineligible individuals can improve survival over BCMA bispecifics like teclistamab,” Song and colleagues concluded in their abstract. “Hence, these patients should be especially considered for early BCMA CAR T.”

References

1. Song J. Real-world comparison of overall survival between BCMA – bispecific and CAR T-cell therapies in multiple myeloma. Presented at: ESMO Congress 2024; September 13-16, 2024; Barcelona, Spain.

2. Mattina C. FDA approves first bispecific antibody, teclistamab, for R/R multiple myeloma. AJMC^®. October 26, 2022. Accessed September 12, 2024. https://www.ajmc.com/view/fda-approves-first-bispecific-antibody-teclistamab-for-r-r-multiple-myeloma

3. McNulty R. FDA approves idecabtagene vicleucel for multiple myeloma. AJMC. March 27, 2021. Accessed September 12, 2024. https://www.ajmc.com/view/fda-approves-idecabtagene-vicleucel-for-multiple-myeloma

4. Caffrey M. FDA approves cilta-cel to treat R/R multiple myeloma. AJMC. March 1, 2022. Accessed September 12, 2024. https://www.ajmc.com/view/fda-approves-cilta-cel-to-treat-r-r-multiple-myeloma

5. Shaw M. FDA approves cilta-cel for earlier treatment of RRMM. AJMC. April 6, 2024. Accessed September 12, 2024. https://www.ajmc.com/view/fda-approves-cilta-cel-for-earlier-treatment-of-rrmm

6. Bonavitacola J. Ide-cel receives approval for earlier treatment for relapsed, refractory multiple myeloma. AJMC. April 5, 2024. Accessed September 12, 2024. https://www.ajmc.com/view/ide-cel-receives-approval-for-earlier-treatment-for-relapsed-refractory-multiple-myeloma