Novel Combination Exceeds Standard Therapy for Relapsed or Refractory Multiple Myeloma

Talquetamab plus teclistamab yields high responses in patients with triple-class exposed, relapsed or refractory multiple myeloma (MM) and extramedullary disease (EMD), according to the phase 2 RedirecTT-1 study.

The results from the EMD cohort were presented at the European Hematology Association 2025 Congress by Shaji Kumar, MD, of the Mayo Clinic.

Ninety patients received talquetamab 0.8 mg/kg once every 2 weeks in addition to teclistamab 3.0 mg/kg once every 2 weeks with step-up dosing. After achieving a very good partial response or better at cycle 4 or cycle 6, patients could switch to dosing once every 4 weeks. The median follow-up was 12.6 months.

Twenty-two percent of patients had high-risk cytogenetics, 39% had nonsecretory/oligosecretory disease, 84% had triple-class refractory and 36% had penta-drug refractory disease, 20% had prior anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy, and 9% had prior bispecific antibodies.

The overall response rate (ORR) was 79% for the entire cohort, 83% for patients with prior anti-BCMA CAR T-cell therapy, and 75% for patients who had prior bispecific antibody therapy. More than half of patients (52%) achieved a complete response or better.

At 9 months, the duration of response was 75%, progression-free survival was 64%, and overall survival was 80%. After switching to once-every-4-week dosing of both talquetamab and teclistamab, more than 90% of patients deepened or maintained the response.

As for safety, 78 patients (87%) experienced grade 3 or 4 adverse events (AEs), most commonly neutropenia (62%). Cytokine release syndrome, all grade 1 or 2, occurred in 70 patients (78%). Immune effector cell–associated neurotoxicity syndrome (ICANS) of grade 4 or lower occurred in 11 patients (12%). Other common AEs included taste changes (79%), skin-related AEs (69%), nail-related AEs (56%), and infections (79%), with 88% of grade 3 or 4 infections occurring within the first 6 months. Eight  patients (9%) discontinued the treatment combination due to AEs.

Dr. Kumar and colleagues concluded, “The phase 2 cohort of RedirecTT-1 is the largest dedicated EMD study to date. Tal [talquetamab] + Tec [teclistamab] led to a high ORR and deep, durable responses; efficacy exceeded standard therapies, including BsAb [bispecific antibody] monotherapies, and was comparable to CAR-T therapies in pts [patients] with RRMM with EMD.”