Novel drug combinations for newly diagnosed multiple myeloma: how can we improve on current regimens?

Multiple myeloma (MM) therapy has greatly evolved over the last decade. Immunomodulators and anti-CD38 antibodies have reshaped the therapeutic landscape. Nevertheless, relapses occur with worsening prognosis each relapse. Achieving deep responses in first-line treatment is key to reducing future disease burden.

To advance patient outcomes, current regimens must be continuously refined through personalization, incorporation of biomarkers to guide therapy, and novel drugs. This review aims to assess existing therapies and investigate how integrating novel drug combinations and biomarker-driven approaches can improve efficacy and tolerability for newly diagnosed multiple myeloma (NDMM) patients. Meta-analysis, systematic reviews, original articles, and real-world studies were included in this review. Databases searched included PubMed, Scopus, and Google Scholar from inception until February 2025.

Discerning the best therapy sequence is a challenge for NDMM individuals. Minimal residual disease assessment is becoming a pivotal tool for guiding therapeutic approaches to enhance outcomes and tolerability. Emerging evidence supports early use of potent therapies - such as next-generation anti-CD38 antibodies and CELMoDs - to achieve deeper, more durable responses and possibly delay relapses. Immunotherapies like bispecific antibodies and CAR-T cells are also being explored in front-line settings, though reducing their infectious complications is still under investigation.