Endless possibilities and how to exploit them? What is the optimal treatment sequence?

Area of Science:

• Hematology/Oncology
• Immunotherapy
• Pharmacology

Background:

• The treatment of multiple myeloma has significantly evolved with novel agents.
• Anti-CD38 monoclonal antibodies (mAbs) and T-cell redirecting immunotherapies have emerged as key players.
• Optimal sequencing of these therapies across the disease continuum is critical for maximizing efficacy.

Purpose of the Study:

• To synthesize evidence from pivotal clinical trials on multiple myeloma therapeutics.
• To guide treatment decisions and optimize the sequencing of novel therapies.
• To address the evolving therapeutic landscape in both frontline and relapsed settings.

Main Methods:

• Review and synthesis of data from key clinical trials in multiple myeloma.
• Analysis of efficacy and toxicity profiles of anti-CD38 mAbs, CAR T-cell therapies, and bispecific antibodies (BsAbs).
• Evaluation of treatment sequencing strategies based on available evidence and emerging data.

Main Results:

• Frontline quadruplet regimens (anti-CD38 mAb, lenalidomide, bortezomib/carfilzomib) are recommended for eligible patients.
• Chimeric antigen receptor T-cell (CAR T) therapies targeting B-cell maturation antigen (BCMA) show superiority in early relapse.
• Bispecific antibodies (BsAbs) targeting BCMA and GPRC5D demonstrate activity in late relapse; CAR T-cell therapy is preferred before BsAbs.

Conclusions:

• Strategic sequencing of novel agents, including CAR T-cell therapies and BsAbs, is essential for improving progression-free survival (PFS).
• Anti-CD38 mAb and carfilzomib-based triplets remain important options for non-refractory patients.
• Further trials are needed to establish optimal sequencing and identify valuable endpoints like PFS-2.