CAR-T cell therapy as second line treatment for high-risk multiple myeloma (MM)

During EHA 2024, Prof Dr Xavier Leleu, Head of the Myeloma Clinic and Head of the Department of Haematology at the University Hospital of Poitiers (France), presented the results of cohort 2B of the KARMMA-2 study. In this study cohort, transplant ineligible multiple myeloma (MM) patients with an early relapse following first line therapy were treated with the anti-CD-19 CAR-T product idecabtagene vicleucel (ide-cel).

The study cohort at hand included 35 MM patients who did not receive an autologous stem cell transplantation in first line and relapsed within 18 months following their diagnosis on a first line treatment regimen including a proteasome inhibitor, an immunomodulatory agent and dexamethasone.  The median age of patients in the study was 60 years, about 40% carried high-risk cytogenetic abnormalities and 67.7% had double-class refractory disease. Overall, 87.1% of patients received bridging therapy prior to CAR-T infusion.

Of the 31 patients who received the CAR-T therapy, 71.0% obtained a complete response following CAR-T therapy (overall response rate: 93.5%). This is a remarkable finding given the fact that the complete response rate in first line was only 3.2%. At data cut-off, 51.6% of patients had an ongoing complete response, with a 24-month duration of response rate among patients with at least a complete response of 75.7% (median not reached). Importantly, this high complete response rate was accompanied by a steady improvement in overall quality of life, pain, and fatigue.

In conclusion, ide-cel demonstrated a favourable benefit-risk profile in transplant-ineligible patients with clinical high-risk MM who experienced an early relapse following first line therapy.