(C-193) Therapeutic Horizon in Multiple Myeloma: Emerging Therapies and Future Perspectives

Background: Recent advancements in multiple myeloma (MM) treatment have enhanced clinical outcomes, promoting longer survival and a shift toward more targeted and tolerable therapies.

Objectives: This study sought to assess the present state of newly MM drug candidates in clinical trials (2013–2024), analyzing their characteristics, targeting strategies, and potential impact on treatment advancements.

Methods: The search strategy utilized ClinicalTrials.gov (CTGR) and Cortellis Drug Discovery Intelligence (CDDI) to identify MM clinical trials conducted between January 1, 2013, and December 31, 2024. The research included studies on therapies indicated for MM treatment (newly diagnosed and refractory), including both active trials and completed studies with results. Data analysis explored the clinical trial landscape and characteristics, assessing their number, phases, status, indications, drug properties, and targets. Descriptive analyses were performed through absolute and relative frequencies. Trends in trial registration and the evolution of active studies were estimated using joinpoint regression and expressed as Annual Percentage Change (APC). Statistical analyses were performed using Python (version 3.12.6) with the SciPy library (version 1.15.1).

Results: A total of 1936 MM clinical trials were identified in CTGR and 5984 in CDDI. After removing duplicates and applying exclusion criteria, 355 trials remained in CTGR and 234 in CDDI. Additionally, 169 active patents were identified in CDDI. Early-phase and Phase 1 trials represented most studies (50.4% in CTGR; 48.7% in CDDI). A consistent upward trend over time (2013-2024) of trial registrations was observed (APC = 1.81, p = 0.01, r = 0.69). The average number of active studies was 18.56 ± 1.54 per year (p < 0.0001), with a significant focus on biologic therapies, representing 71.8% (n=255) of investigational molecules in CTGR and 77.4% (n=181) in CDDI. Among these, advanced gene therapies, including CAR-T cell therapies, comprised 47.6% of trials in CTGR and 38.5% in CDDI. Eight investigational therapies in active phase 3 trials for relapsed or refractory multiple myeloma were identified across the databases. These include cereblon modulators (mezigdomide, iberdomide), bispecific T-cell engagers (etentamig, linvoseltamab, SG-301, felzartamab), and CAR-T cell therapies (anitocabtagene autoleucel, arlocabtagene autoleucel), targeting key molecules such as BCMA, GPRC5D, CD38, IKZF1, and IKZF3.

Conclusions: The growing number of MM clinical trials underscores continuous research efforts. Early-phase studies predominate, with biologic therapies — particularly monoclonal antibodies and CAR-T cells — driving advancements toward more targeted and personalized MM treatments.