A recent study presented at the ESMO Congress 2024 compared the efficacy of CAR T-cell therapies and bispecific antibodies in treating multiple myeloma, revealing that CAR T-cell therapy is associated with improved overall survival compared to bispecific antibodies like teclistamab. The research, which analyzed real-world data, suggests a potential shift in treatment strategies for multiple myeloma patients, particularly those ineligible for bone marrow transplantation.
Superior Survival with CAR T-cell Therapy
The study, led by Junmin Song, MD, utilized the TriNetX US Collaborative Network database, encompassing over 100 million patients from more than 60 healthcare organizations. The analysis included 391 patients who received CAR T-cell therapy (277 with ide-cel and 114 with cilta-cel) and 458 patients treated with teclistamab. The mean age of the patients was 66 years, and 54% were male. After propensity score matching, the study compared 180 patients receiving ide-cel with 180 receiving teclistamab, and 93 patients receiving cilta-cel with 93 receiving teclistamab.
The results indicated a significantly lower mortality rate in the CAR T cohort (20%) compared to the teclistamab cohort (30%) after up to one year of follow-up. The CAR T cohort also demonstrated significantly lower all-cause mortality at 3, 6, and 12 months. At 12 months, the hazard ratio (HR) for all-cause mortality was 0.62 (95% CI, 0.38-0.99), favoring CAR T-cell therapy.
Safety Profile and Patient Selection
While CAR T-cell therapy demonstrated superior survival outcomes, it was associated with a higher risk of cytokine release syndrome (CRS) compared to teclistamab (50% vs 40%). However, CRS events primarily occurred within the first month of therapy initiation. There were no significant differences in neurotoxicity between the two treatment groups, with approximately 20% of patients in both cohorts experiencing neurotoxic effects, also predominantly within the first month.
Further analysis revealed that older patients (≥ 70 years) and those who did not undergo bone marrow transplantation experienced greater benefits from CAR T-cell therapy, exhibiting improved overall survival.
Implications and Future Directions
Despite the promising findings, the study authors acknowledged several limitations, including the inability to distinguish between newly diagnosed and relapsed disease and the lack of stratification for standard versus high-risk multiple myeloma. Additionally, potential miscoding within the International Classification of Diseases, Tenth Revision, and the TriNetX codes could have influenced the results.
Despite these limitations, the study's findings suggest that CAR T-cell therapy may offer a survival advantage over bispecific antibodies in specific multiple myeloma patient populations. "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. "Hence, these patients should be especially considered for early BCMA CAR T."
