Large Real-World Study Validates Idecabtagene Vicleucel Outcomes Seen in KarMMa Trial

Idecabtagene vicleucel (ide-cel, Abecma; Bristol Myers Squibb) in relapsed or refractory multiple myeloma (RRMM) demonstrated favorable safety and efficacy in the largest real-world study in this patient population, mirroring clinical outcomes observed in the KarMMa clinical trial (NCT03361748). The data were published by Surbhi Sidana, MD, associate professor of medicine at Stanford University, et al in Blood.^1,2

3D rendering of a CAR T cell | Image Credit: © furyon - stock.adobe.com

Ide-cel is the first FDA-approved chimeric antigen receptor (CAR) T-cell therapy indicated for adult patients with relapsed or refractory MM after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The decision was based on positive results from the phase 2 KarMMa trial, which showed ide-cel had overall response rates (ORR) of approximately 70% and 85% overall response rates in younger and older patients, respectively.³

However, due to the selectivity of clinical trials, there is little conclusive evidence of real-world outcomes for patients with RRMM receiving standard-of-care ide-cel.⁴

“Although the approval of ide-cel was widely celebrated, a major question was whether similar efficacy would be seen among patients outside of the clinical trial setting,” the authors wrote.⁴

The authors assessed 821 recipients of ide-cel using the Center for International Blood and Marrow Transplant Research registry. The cohort's median age was 66 years, 31% of patients were over 70, 15% were Black, 7% were Hispanic, and 77% had at least 1 severe comorbidity. Fifteen percent of patients had previously undergone BCMA-directed therapy, 17% had extramedullary illness, 27% had high-risk cytogenetics, and the median number of previous lines of therapy was 7.⁴

At the median follow-up of 11.6 months, ide-cel treatment yielded an overall response rate of 73% with a complete response of 25%. Additionally, the authors reported a progression-free survival of 8.8 months.⁴

The safety profile showed cytokine release syndrome (CRS) as the most common adverse event (AE) in 80% of patients, of which 3% experienced grade 3 or higher CRS. Immune effector cell–associated neurotoxicity syndrome was less common but observed in 28% (grade ≥3, 5%). Approximately 45% of patients experienced clinically significant infections. Second primary malignancies were reported in 4%, including 1% myeloid malignancies. Notably, only 6% of the patient population died as a result of treatment-related AEs.⁴

“Although the data in this CIBMTR analysis cannot distinguish the relative benefit of ide-cel compared with alternative therapies, clinicians now have a robust data set from a large cohort of patients confirming that ide-cel is an effective and relatively well-tolerated CAR T therapy, even in the setting of significant comorbidities that may preclude clinical trial enrollment,” Sidana and their fellow investigators concluded. “Furthermore, ide-cel is optimally used when patients have adequate LD, no prior BCMA exposure, and good disease control at the time of CAR T infusion.”⁴

REFERENCES

1. Efficacy and safety study of bb2121 in subjects with relapsed and refractory multiple myeloma (KarMMa). Updated May 23, 2025. Accessed July 15, 2025. https://clinicaltrials.gov/study/NCT03361748

2. Sidana S, Ahmed N, Akhtar O, et al. Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma. Blood. July 10, 2025. Doi:10.1182/blood.2024026216

3. Gerlach A. Study shows comparable safety, efficacy of idecabtagene vicleucel in older patients. Pharmacy Times. December 3, 2024. Accessed July 15, 2025. https://www.pharmacytimes.com/view/study-shows-comparable-safety-efficacy-of-idecabtagene-vicleucel-in-older-patients

4. Schmidt T. Real-world data provide a CARbon copy for ide-cel. Blood. July 10, 2025. Doi:10.1182/blood.2025029274