Teclistamab-Daratumumab Outperforms Standard of Care for R/R Multiple Myeloma

Late-breaking data presented at ASH 2025 demonstrated that the combination of teclistamab plus daratumumab for multiple myeloma produced some of the most impressive hazard ratios seen in this patient population to date, outperforming standard-of-care regimens such as DPd (daratumumab, pomalidomide, dexamethasone) or PVd (pomalidomide, bortezomib, dexamethasone). Patients who were not previously exposed to or refractory to daratumumab showed particularly high progression-free survival (PFS) rates, with durable responses extending even to the 3-year mark. The dual mechanism of combining a BCMA-targeting bispecific antibody with an anti-CD38 monoclonal antibody is thought to enhance tumor cell killing while also modulating the immune microenvironment by reducing regulatory cells and recruiting natural killer (NK) cells.

This discussion also explores how these data might influence treatment sequencing. While the efficacy of the teclistamab-daratumumab combination is notable, the widespread use of anti-CD38 therapy in current clinical practice, including in earlier lines and smoldering myeloma, raises questions about applicability to real-world patient populations. CAR T-cell therapy remains the preferred early-line approach in eligible patients, largely because earlier use allows infusion into less-exhausted T cells, resulting in better expansion, persistence, and durable responses. Bispecific combinations like teclistamab plus daratumumab may be particularly valuable in relapsed or refractory patients, improving response rates and PFS, but their optimal sequencing relative to CAR T therapy requires careful consideration.

Overall, new data reinforce the promise of combining bispecific antibodies with anti-CD38 therapy in relapsed/refractory multiple myeloma, demonstrating strong efficacy and durable responses while highlighting ongoing questions about integration into treatment sequencing and the timing of subsequent CAR T therapy. These findings underscore the evolving landscape of immunotherapy strategies and the importance of tailoring approaches to individual patient histories and immune fitness.