FDA Approves Teclistamab Plus Subcutaneous Daratumumab for Relapsed/Refractory Multiple Myeloma

The FDA has approved teclistamab-cqyv (Tecvayli) in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy.¹

The FDA also converted the approval of teclistamab monotherapy for the treatment of patients with relapsed/refractory multiple myeloma from accelerated to traditional status.

The regulatory decision was supported by data from the phase 3 MajesTEC-3 trial (NCT05083169), which were previously presented at the 2025 ASH Annual Meeting. Findings demonstrated that at a median follow-up of 34.5 months, patients treated with teclistamab plus daratumumab (n = 291) achieved a median progression-free survival (PFS) that was not reached compared with 18.1 months for those given investigator’s choice of daratumumab plus pomalidomide (Pomalyst) and dexamethasone (DPd) or daratumumab plus bortezomib (Velcade) and dexamethasone (DVd; n = 296; HR, 0.17; 95% CI, 0.12-0.23; P < .0001).² The respective 36-month PFS rates were 83.4% vs 29.7%.

The overall response rate (ORR) was 89.0% with teclistamab plus daratumumab compared with 75.3% with DPd or DVd (odds ratio [OR], 2.65; 95% CI, 1.68-4.18; P < .0001). Complete response (CR) or better rates were 81.8% vs 32.1%, respectively (OR, 9.56; 95% CI, 6.47-14.14; P < .0001). Minimal residual disease (MRD)–negativity rates at a sensitivity of 10⁻⁵ were 58.4% in evaluable patients receiving the teclistamab-based combination compared with 17.1% in patients in the control arm (OR, 6.78; P < .0001).

The median overall survival (OS) was not reached in either arm; however, an improvement was observed with teclistamab plus daratumumab (HR, 0.46; 95% CI, 0.32-0.65; P < .0001). The 36-month OS rates were 83.3% for the combination vs 65.0% for DPd or DVd.

How was the MajesTEC-3 trial designed?

MajesTEC-3 was a randomized, open-label, phase 3 study that enrolled patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy, including a proteasome inhibitor and lenalidomide. Patients who had received only 1 prior line were required to be refractory to lenalidomide, according to International Myeloma Working Group criteria. An ECOG performance status of 0 to 2 was required, and patients were excluded if they had received prior BCMA-directed therapy or were refractory to anti-CD38 monoclonal antibodies.

Patients were randomly assigned 1:1 to receive teclistamab plus daratumumab or investigator’s choice of DPd or DVd; notably, 91% of patients in the control arm received DPd.

PFS per independent review committee assessment served as the primary end point. Secondary end points included CR or better rate, ORR, MRD-negativity rate, OS, symptom score, safety, and pharmacokinetics/immunogenicity.

What were the safety data for teclistamab plus daratumumab?

The safety profile of teclistamab plus daratumumab was consistent with the known safety profiles of each agent. Any-grade treatment-emergent adverse effects (TEAEs) occurred in 100% of patients in both arms, with grade 3 or 4 TEAEs reported in 95.1% of patients receiving the combination vs 96.6% of those in the control arm. TEAEs led to treatment discontinuation in 4.6% and 5.5% of patients, respectively. Serious adverse effects occurred in 70.7% and 62.4% of patients, and TEAEs led to death in 7.1% vs 5.9% of patients, respectively.

The most common hematologic TEAEs in the experimental arm included neutropenia (78.4%), anemia (39.2%), thrombocytopenia (36.4%), lymphopenia (22.3%), and leukopenia (18.0%). Common nonhematologic TEAEs included cytokine release syndrome (CRS; 60.1%), diarrhea (51.9%), cough (48.1%), and pyrexia (36.7%).

CRS events were primarily grade 1, occurring in 44.2% of patients; grade 2 CRS occurred in 15.9% of patients, and no grade 3 or higher CRS was reported. All CRS events resolved, and no grade 2 or higher events were observed after the first cycle.

What is the recommended dosing for teclistamab plus daratumumab?

Teclistamab is administered via step-up dosing followed by a full dose of 3 mg/kg beginning in cycle 3, initially every 2 weeks through cycle 6 and then once every 4 weeks thereafter. Subcutaneous daratumumab is administered at 1800 mg weekly during cycles 1 and 2, every 2 weeks during cycles 3 through 6, and every 4 weeks starting in cycle 7, with dexamethasone premedication during cycle 1.

References

1. FDA grants third approval under the national priority voucher program. FDA. March 5, 2026. Accessed March 5, 2026. https://www.fda.gov/news-events/press-announcements/fda-grants-third-approval-under-national-priority-voucher-program
2. Mateos M-V, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): results of majestec-3. Blood. 2025;146(suppl 2): LBA-6. doi:10.1182/blood-2025-LBA-6