Impact of Bridging Therapy and BCMA Exposure on Ide-Cel Outcomes in Myeloma

In a recent Case-Based Roundtable event in Durham, North Carolina, Dr. Samuel M. Rubinstein, an associate professor of medicine at the University of North Carolina School of Medicine, discussed critical findings from the KarMMa-3 trial and real-world patient outcomes regarding the use of idecabtagene vicleucel (ide-cel) in treating multiple myeloma. The focus was on the significance of bridging therapy and prior exposure to B-cell maturation antigen (BCMA) therapies, elements that appear to influence patient responses to CAR T-cell therapy.

The KarMMa-3 trial (NCT03651128) provided insights into how bridging therapy can impact the effectiveness of CAR T-cell treatments. According to Dr. Rubinstein, patients who were triple-class exposed and received bridging therapy exhibited a median progression-free survival (PFS) of 20.7 months, a notable improvement compared to those who did not receive such therapy. He stated, "Whether the bridging therapy itself improved PFS or if these patients are inherently lower risk remains to be fully understood. However, successful bridging seems to correlate with better outcomes."

Further analysis revealed that the specific type of bridging therapy administered also played a significant role. Carfilzomib, combined with dexamethasone, emerged as the most effective option among various bridging therapies. This observation aligns with data indicating that daratumumab-refractory patients tend to have less favorable outcomes with non-daratumumab-based regimens.

The quality of life (QoL) of patients undergoing CAR T-cell therapy also showed significant improvement post-treatment. Dr. Rubinstein highlighted that most disease-related symptoms improve within months following CAR T-cell administration, contributing to enhanced emotional and physical functioning.

Real-world evidence corroborated findings from the KarMMa-3 trial. A study conducted by Dr. Christopher Ferreri, previously at The University of Texas MD Anderson Cancer Center and now at Atrium Health Levine Cancer Institute, assessed the outcomes of patients who had prior BCMA therapy. The analysis indicated that while patients without previous BCMA exposure had an 88% response rate to ide-cel, those who had received BCMA therapies previously still demonstrated a substantial response rate of 74%. This suggests that prior BCMA therapy does not categorically preclude patients from benefiting from subsequent BCMA-targeted treatments.

Dr. Ferreri's findings also noted that patients who underwent prior treatments with antibody-drug conjugates exhibited the lowest response rates, whereas those with previous CAR T or bispecific therapies showed promising outcomes, reinforcing the notion that the sequencing of therapies is vital for optimizing patient care.

The implications of these findings extend beyond individual treatment success; they underscore the necessity for personalized treatment strategies in multiple myeloma, particularly as CAR T-cell therapies become more prevalent. As Dr. Rubinstein concluded, understanding the nuances of bridging therapy and BCMA exposure will enable clinicians to better tailor therapies to individual patient profiles, ultimately enhancing the efficacy of CAR T-cell treatment in relapsed and refractory multiple myeloma.

This Case-Based Roundtable discussion forms part of a broader initiative aimed at improving treatment outcomes for multiple myeloma patients and highlights the ongoing need for research and clinical trials that focus on patient-centric care strategies.