Phase 2 results of the RedirecTT-1 study showed that treatment with talquetamab and teclistamab in patients with drug-resistant, true extramedullary myeloma induced a response in 79%. The 12-month overall survival rate was 74%.
“Our findings offer valuable data for treatment in a population that is both clinically challenging and underrepresented in existing clinical studies,” wrote lead author Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues, who published their findings in The New England Journal of Medicine.
Phase 1 results of the study showed that the combination of the anti-GPRC5D bispecific antibody talquetamab and the anti-B-cell maturation antigen (BCMA) teclistamab was efficacious in this patient population that often faces an increased risk of progression, relapse, and poorer outcomes.
This multicenter, nonrandomized, open-label study included 90 patients (median age, 64.5 years) with drug-resistant, true extramedullary myeloma who were followed for a median of 12.6 months. Patients had received a median of four prior therapies; 20% (n=18) had received anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, and 9% (n=8) previously received bispecific antibodies. Patients were treated with subcutaneous talquetamab 0.5 mg/kg of body weight and teclistamab 3.0 mg/kg every other week in 28-day cycles.
At data cutoff, more than half of patients (54%; n=49) were still receiving treatment. The researchers said the number of responders (n=71) was “substantially greater than the hypothesized 40%.” Among responders, 64% had at least a 12-month duration of response, and the median response duration was 13.8 months. The 12-month progression-free survival was 61%. Median time to first response was 2.6 months, and median time to best response was 4.7 months.
Responses were similar across subgroups, including those who:
- Received three or more prior lines of therapy
- Had International Staging System stage III disease
- Received four or more extramedullary sites at baseline
- Had high-risk cytogenetics
Among those previously treated with CAR-T and bispecific therapies, 15 and five patients, respectively, had a very-good partial response or better.
The most common any-grade adverse events (AEs) were oral symptoms (87%); cytokine release syndrome (78%); and non-rash skin events (69%).
Grade 3/4 hematologic AEs occurred in 76% of patients, and 31% experienced grade 3/4 infection. The rate of these AEs was “consistent with previous observations for each agent as monotherapy,” the authors noted, and no new safety signals were reported.
Six percent of patients discontinued one or both therapies, and 10 deaths (11%) occurred, five of which were deemed related to the study treatment.
The study is limited by its short duration of follow-up and single-group, open-label study design.
“These results show clinical benefit from this off-the-shelf, bispecific antibody combination and validate dual targeting of GPRC5D and BCMA with talquetamab plus teclistamab as a potential therapeutic approach in myeloma,” the authors concluded.
The study was supported by Johnson & Johnson.
Reference
Kumar S, Mateos MV, Ye JC, et al; RedirecTT-1 Investigators Study Group. Dual targeting of extramedullary myeloma with talquetamab and teclistamab. N Engl J Med. 2026;394(1):51-61. doi:10.1056/NEJMoa2514752
