Belantamab mafodotin does not induce B-cell maturation antigen loss or systemic immune dysfunction in multiple...

Area of Science:

• Oncology
• Immunotherapy
• Pharmacology

Background:

• B-cell maturation antigen (BCMA) is a target for multiple myeloma therapies, including CAR-T cells, bispecific antibodies (bsAbs), and antibody-drug conjugates (ADCs).
• T-cell exhaustion and target antigen loss can limit the efficacy of current BCMA-targeting treatments.
• Optimal sequencing of BCMA-targeting therapies is crucial for improving long-term outcomes in multiple myeloma.

Purpose of the Study:

• To evaluate the impact of belantamab mafodotin on BCMA levels, binding affinity, and immune cell fitness in multiple myeloma patients.
• To determine the potential of belantamab mafodotin for sequencing ahead of other BCMA-targeting therapies.

Main Methods:

• Analysis of clinical data from studies involving belantamab mafodotin (monotherapy and combination regimens).
• Measurement of soluble BCMA (sBCMA) levels and belantamab mafodotin binding to sBCMA using electrochemiluminescence.
• Assessment of T-cell and natural killer (NK) cell counts and expression of functional, exhaustion, and proliferation markers.

Main Results:

• Soluble BCMA levels decreased at best response but returned to baseline at progression.
• Belantamab mafodotin binding to BCMA remained unaffected, indicating no impact on the target epitope.
• No significant changes were observed in T-cell/NK cell counts or expression of exhaustion, costimulatory, proliferation, or antitumor activity markers.

Conclusions:

• Belantamab mafodotin treatment did not impair BCMA binding or T-cell/NK cell fitness.
• These findings support the potential use of belantamab mafodotin earlier in the treatment sequence for multiple myeloma.
• Further confirmatory studies are warranted to establish optimal sequencing strategies.