Raab: Utilizing Early Bispecific Combos in Myeloma

The phase 2 MajesTEC-5 study (NCT05695508) has yielded highly encouraging results for a novel, immune-based combination therapy in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The investigational regimen evaluated the BCMA-targeting bispecific antibody teclistamab-cqyv (Tecvayli) in combination with daratumumab (Darzalex Faspro) and standard-of-care agents lenalidomide or bortezomib.

The rationale for moving bispecific antibodies into the frontline setting is to leverage the robust and uncompromised T-cell function of treatment-naïve patients. The updated analysis, encompassing 50 patients, demonstrated profound clinical efficacy, with 100% of patients achieving an overall response rate following induction therapy. Furthermore, an exceptionally deep level of response was achieved, as 100% of evaluable patients reached minimal residual disease (MRD) negativity at the 10^-5 or 10^-6 threshold after 6 cycles of treatment, and almost all patients achieved a complete response.

The treatment combination exhibited a manageable safety profile. While cytokine release syndrome was observed in 65% of patients, all cases were low grade (grade 1 or 2). Importantly, no cases of immune effector cell–associated neurotoxicity syndrome or grade 5 toxicities were reported, and no patients discontinued treatment due to toxicity. The rate of grade 3 or higher infections was 36%, concentrated mainly within the first 3 cycles.

These findings underscore the potential of this combination as a highly effective, steroid-sparing frontline option. Future research will focus on longer follow-up to confirm that these impressive early responses translate into sustained disease-free survival. A key goal for subsequent trials is to determine if the treatment duration can be limited, perhaps to 2 years, to provide patients with valuable treatment-free intervals.