High Response Rates With Talquetamab Plus Teclistamab in Triple-Class Refractory Multiple Myeloma

Talquetamab-tgvs (Talvey; Johnson & Johnson) and teclistamab-cqyv (Tecvayli; Johnson & Johnson) yielded statistically significant overall response rates (ORR) and durability in patients with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) with extramedullary disease in the phase 2 RedirecTT-1 study (NCT04586426).¹

Visualization of multiple myeloma cells | Image Credit: © Tongpoon - stock.adobe.com

MM is an incurable, highly heterogeneous hematologic malignancy characterized by the proliferation of B lymphocytes in the bone marrow, leading to anemia, renal failure, and brittle bones. Historically, MM is difficult to treat, and continued treatment yields poorer responses with each line of therapy. Identifying and targeting highly expressed proteins, such as BCMA or GPRC5D, on the surface of myeloma cells has led to increasingly better outcomes and longer remission for many patients.²

The emergence of such biomarkers led to the development of agents such as bispecific T-cell engagers—namely, talquetamab and teclistamab, which target GPRC5D and BCMA, respectively. Both agents received FDA approval for the treatment of patients with RRMM who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.²

As a combination therapy, talquetamab and teclistamab show significant promise in the phase 1b/2 dose escalation and expansion in the RedirecTT-1 trial (NCT04586426). The investigators assessed a total of 90 patients who received talquetamab at a dosage of 0.8 mg/kg once every 2 weeks plus teclistamab at a dosage of 3.0 mg/kg every 2 weeks. Of the participants, 22% had high-risk cytogenetics, 39% had nonsecretory or oligosecretory disease, and the median number of soft tissue plasmacytomas was 2 (range: 1–14). Patients had received a median of 4 prior lines of therapy; 84% were triple-class refractory, 36% were penta-drug refractory, 20% had prior anti-BCMA chimeric antigen receptor (CAR) T therapy, and 9% had received prior bispecific antibodies.^1-3

At the median follow-up of 12.6 months, there was an ORR of 79% (95% CI, 69.0–86.8), including a complete response rate of 52%. Patients with prior anti-BCMA CAR-T therapy achieved an ORR of 83% (n = 15) and 75% for those with prior bispecific therapy (n = 6). At 9 months, duration of response was 75%, progression-free survival was 64%, and overall survival was 80%.³

Grade 3 or 4 adverse events (AEs) occurred in 87% of patients. Cytokine release syndrome was seen in 78% (all grade 1 or 2), immune effector cell-associated neurotoxicity syndrome occurred in 12% (1% each grade 3 and 4; no grade 5), and neutropenia in 62% of trial participants. The investigators also reported mild AEs such as taste changes (79%), skin issues (69%), and nail changes (56%)—which were common but mild (grade 1 or 2)—as well as rashes (29%).³

"The investigational combination of [talquetamab] and [teclistamab] has demonstrated deep, durable responses in patients with [RRMM] and now shows great promise in those with extramedullary myeloma, where standard therapies often fall short," Yael Cohen, MD, Head of Myeloma Unit, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel, said in a press release. "Dual targeting of GPRC5D and BCMA may lead to a higher ORR and greater depth of response by mitigating target antigen-related escape. The RedirecTT-1 trial shows the power of this novel dual-targeting combination approach as a potential treatment option for patients with this disease."²

REFERENCES

1. A study of the combination of talquetamab and teclistamab in participants with relapsed or refractory multiple myeloma (RedirecTT-1). ClinicalTrials.gov identifier: NCT04586426. Updated May 23, 2025. Accessed June 16, 2025. https://clinicaltrials.gov/study/NCT04586426

2. Investigational combination of first-in-class bispecifics TALVEY® and TECVAYLI® shows deep and durable responses in heavily pretreated multiple myeloma patients with extramedullary disease. PR Newswire. June 15, 2025. Accessed June 16, 2025. https://www.prnewswire.com/news-releases/investigational-combination-of-first-in-class-bispecifics-talvey-and-tecvayli-shows-deep-and-durable-responses-in-heavily-pretreated-multiple-myeloma-patients-with-extramedullary-disease-302481737.html

3. Phase 2 study of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma and extramedullary disease: REDIRECTT-1. European Hematology Association 2025 Congress. June 12, 2025, to June 15, 2025. Milan, Italy. Abstract LB4001