Unprecedented Efficacy in the MajesTEC-3 Trial in Multiple Myeloma: Ajay K. Nooka, MD, MPH

On March 5, the FDA expanded the approval of teclistamab (Tecvayli) to a full traditional approval for adult patients who have received at least 4 prior lines of therapy, as well as for its use in combination with daratumumab hyaluronidase-fihj (Darzalex Faspro), both from Janssen Biotech, Inc, to treat patients with relapsed or refractory multiple myeloma (R/R MM)—a regulatory milestone allows the combination to be used as early as the second line of therapy for patients who have received at least 1 prior line of treatment, including a proteasome inhibitor and an immunomodulatory agent.

The approval is supported by data from the phase 3 MajesTEC-3 trial (NCT05083169), a confirmatory study that randomized 587 patients to receive either the subcutaneous teclistamab-daratumumab combo or an investigator’s choice of standard triplets: daratumumab, pomalidomide (Pomalyst), and dexamethasone (DPd) or daratumumab, bortezomib (Velcade), and dexamethasone (DVd). Investigator Ajay K. Nooka, MD, MPH, describes the trial results as “unprecedented,” highlighting an HR of 0.17 in this interview with The American Journal of Managed Care^®. Nooka is a professor in the Department of Hematology and Medical Oncology, director of the Myeloma Program, and associate director of clinical research at the Winship Cancer Institute, Emory University School of Medicine.

Clinical data showed that 83% of patients in the treatment arm were progression free at the 3-year mark, compared with just 30% in the control arm. Nooka notes that these results are difficult to replicate and demonstrate how the benefit of highly effective therapies extends significantly when moved from later lines to early lines of therapy.

Beyond progression-free survival, the combination showed deep clinical responses. The overall response rate was 89%, with 81.8% of patients achieving a complete response or better. Additionally, 58.4% of patients achieved minimal residual disease negativity, a stark contrast to the 17.1% seen in the control group.

Regarding safety, although the teclistamab arm had higher rates of infections vs the control arm (96.5% vs 84.1%), grade 3 infections notably decreased after the first 6 months of treatment. Cytokine release syndrome was reported in 60.1% of patients, but all cases were low-grade, and no patient had to discontinue treatment because of it.

Looking toward the future, Nooka reassures that even if a patient eventually relapses after this early-line intervention, the pipeline for myeloma remains robust. Researchers are currently evaluating newer targets such as GPRC5D (via bispecifics and chimeric antigen receptor T-cell therapies and FcRH5. This “multitarget approach” ensures that patients will continue to have therapeutic options long after their initial treatment with BCMA-targeted bispecifics.

Reference

Shaw ML. Teclistamab combo approved by FDA for R/R MM. AJMC^®. March 5, 2026. Accessed March 13, 2026. https://www.ajmc.com/view/teclistamab-combo-approved-by-fda-for-r-r-mm