Clinical features associated with poor response and early relapse following BCMA-directed therapies in multiple...

Area of Science:

• Oncology
• Hematology
• Immunotherapy

Background:

• Three classes of BCMA-directed therapies (BDTs) exist: antibody drug-conjugates (ADCs), CAR-T, and T-cell engagers (TCEs).
• Each BDT class has distinct strengths and weaknesses, necessitating guidance for clinical selection.
• Patient characteristics and prior treatment history influence BDT outcomes.

Purpose of the Study:

• To compare the efficacy and safety of different BCMA-directed therapies (BDTs) in multiple myeloma.
• To aid clinicians in selecting the optimal BDT based on patient profiles and treatment history.
• To analyze the impact of prior BDT exposure on subsequent treatment outcomes.

Main Methods:

• Retrospective review of 339 multiple myeloma patients treated with commercial or investigational BDTs at Mayo Clinic (2018-2023).
• Analysis of 385 BDTs administered, including ADCs (n=59), TCEs (n=134), and CAR-T (n=192).
• Progression-free survival (PFS) and overall survival (OS) were compared using adjusted hazard ratios (aHR), controlling for key clinical factors.

Main Results:

• CAR-T and TCEs demonstrated significantly better PFS and OS compared to ADCs, even after adjusting for age, extramedullary disease, and prior treatments.
• Prior BDT exposure negatively impacted outcomes across all BDT classes, particularly for CAR-T therapy.
• Extramedullary disease was a common relapse pattern (54%), with a quarter of these cases lacking prior EMD history.

Conclusions:

• CAR-T therapy shows superior efficacy and should be considered the initial BDT when feasible.
• For patients with prior BDT exposure or rapidly progressive disease, alternative treatment strategies may be warranted.
• Understanding relapse patterns, especially extramedullary disease, is crucial for optimizing BDT selection and management.