Class comparison of BCMA-directed therapies in relapsed multiple myeloma

This retrospective study evaluated the efficacy of BCMA-directed therapies in relapsed multiple myeloma (MM) patients, focusing on antibody drug conjugates (ADCs), T cell engagers (TCEs), and CAR T cells. A total of 385 patients treated at Mayo Clinic between April 2018 and June 2023 were included, with median follow-up of 20 months. CAR T therapy demonstrated superior outcomes with higher overall response rates (86%) compared to ADCs (27%) and TCEs (50%). Patients receiving CAR T also experienced significantly improved progression-free survival (PFS) and overall survival (OS) compared to ADCs and TCEs, adjusting for age, risk stratification (R-ISS), and other factors. However, patients with plasma cell leukemia (PCL) or extramedullary disease (EMD) showed poor median PFS across all therapeutic classes. This study underscores the varying efficacy and challenges associated with different BCMA-targeted therapies in the management of relapsed multiple myeloma, emphasizing the superior outcomes observed with CAR T therapy in this patient cohort.

Key Points:

– Study Population: 385 multiple myeloma patients treated with BCMA-targeted therapies.
– Therapeutic Classes: ADCs (n=59), TCEs (n=134), CAR T (n=192).
– Treatment Duration: Median 1.9 months (ADCs), 3.5 months (TCEs).
– Response Rates: 27% (ADCs), 50% (TCEs), 86% (CAR T).
– Survival Outcomes: CAR T associated with improved PFS and OS compared to ADCs and TCEs.
– High-Risk Subgroups: Poor outcomes observed in patients with plasma cell leukemia or extramedullary disease.
– Mode of Relapse: Extramedullary disease common at relapse.
– Factors Influencing Treatment: Age, cytogenetic abnormalities, refractoriness to multiple classes, and prior lines of therapy impact outcomes.
– Implications: BCMA-directed CAR T therapy offers superior survival benefits, particularly in refractory cases, despite challenges with high-risk features and disease progression.

Authors:
Rees J. Matthew, Aytaj Mammadzadeh, Abiola Bolarinwa, Mohammed E Elhaj, Arwa Bohra, Sikander Ailawadhi, Ricardo Parrondo, Saurabh Chhabra, Yi Lin, Moritz Binder, Suzanne R. Hayman, Angela Dispenzieri, Francis Buadi, David Dingli, Rahma M. Warsame, Radhika Bansal, Prashant Kapoor, Morie A. Gertz, Eli Muchtar, Shaji Kumar

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