Tecvayli Treatment Combo Improves Outcomes in Relapsed/Refractory Myeloma

Treatment with Tecvayli (teclistamab-cqyv) plus Darzalex Faspro (daratumumab and hyaluronidase-fihj; subcutaneous daratumumab) led to meaningful improvements in both overall survival and progression-free survival versus standard daratumumab-based treatments in people with relapsed/refractory multiple myeloma who had received up to three prior treatments, according to results from the phase 3 MajesTEC-3 trial presented at the 2025 ASH Annual Meeting.

The 36-month overall survival rate was 83.3% with Tecvayli plus Darzalex Faspro (Tec-Dara) versus 65% with investigator’s choice of Darzalex Faspro plus dexamethasone and either (DPd) or bortezomib (DVd).

At a median follow-up of 34.5 months the median progression-free survival had not been reached with Tec-Dara versus 18.1 months with DPd/DVd. The 36-month progression-free survival rates were 83.4% versus 29.7%.

The depth of response was also greater with Tec-Dara. The duration of response was not yet evaluable for Tec-Dara compared with 23.5 months with DPd or DVd. Moreover, 81.8% of patients receiving Tec-Dara achieved a complete response or better compared with 31.1% with DPd or DVd. Among evaluable patients the minimal residual disease negativity rate was 89.3% versus 63%.

“MajesTEC-3 showed unprecedented efficacy supporting a new second line and later standard of care with broad potential across academic and community settings” said lead study author Dr. María-Victoria Mateos, of Hospital Universitario de Salamanca, in Salamanca, Spain.

Tec-Dara Safety Profile Shows Manageable Side Effects and Low Neurotoxicity

The safety profile for Tec-Dara showed that all cases of cytokine release syndrome were grade 1 (44.2%) or grade 2 (15.9%) and all cases were resolved. The rate of immune effector cell-associated neurotoxicity syndrome was low with Tec-Dara at 1.1%. The most common hematologic side effect with Tec-Dara was any grade neutropenia at 78.4% versus 82.8% with DPd/DVd. The most common nonhematologic side effects were infections which occurred at grade 3/4 rates of 54.1% versus 43.4% in the Tec-Dara versus control arms.

Mateos noted that the rates of infections were much higher with Tec-Dara versus the control arm during the first 6 months although “beyond month 6 the incidence of infections was comparable and what’s especially important is that the overall incidence of infection declined over time.”

Explaining the reason for the decrease in infections over time Mateos said “The study was initiated before the approval of Tecvayli when we did not yet have any peer-reviewed guidelines for the management of patients with bispecific monoclonal antibodies. When we observed this rate of infections especially during the first 6 months the trial protocol was amended and it was reinforced that investigators should use immunoglobulin replacement therapy and antimicrobial prophylaxis.”

At the time of the study analysis 71% of patients remained on Tec-Dara. Fewer patients discontinued Tec-Dara at 4.6% versus 5.5% who discontinued DPd/DVd in the control arm. Fewer patients died in the Tec-Dara arm at 15.9% versus 33.1%.

Robust Phase 3 Design Confirms Tec-Dara Efficacy in Relapsed/Refractory Multiple Myeloma

The phase 3 MajesTEC-3 trial enrolled patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy including a proteasome inhibitor and lenalidomide (Revlimid). Patients who had received only 1 prior line had to be lenalidomide refractory per International Myeloma Working Group criteria and all patients had to have an ECOG performance status of 0 to 2. Patients were not eligible to enroll if they had previously received BCMA-directed therapy or if they were refractory to anti-CD38 monoclonal antibodies.

Overall, 587 patients were randomized from October 22 2021 to September 29 2023. The median patient age was 65 years and the median number of prior lines of therapy was 2. There were 291 patients randomized to Tec-Dara and 296 patients randomized to DPd (269 patients) or DVd (27 patients).

Following the approved step-up dose schedule patients in the experimental arm received Tecvayli at 1.5 mg/kg weekly in cycles 1 and 2 followed by 3 mg/kg every 2 weeks in cycles 3 to 6 and 3 mg/kg every 4 weeks in cycle 7 onward. The cycles were 28 days. Darzalex Faspro was administered at 1800 mg every week for cycles 1 and 2 every 2 weeks for cycles 3 to 6 and every 4 weeks for cycles 7 onward. In the control arm patients received investigator’s choice of DPd or DVd according to the approved schedules of the regimens.

Commenting on the Tec-Dara regimen Mateos said “It is important to note that the combination of Tecvayli plus Darzalex Faspro is a subcutaneous administration with a convenient monthly dosing after cycle 6 and the combination is free of steroids after cycle 1 day 8 and this is all extremely important from the patient perspective.”

The primary end point was progression-free survival per independent review committee. Secondary end points included overall survival response minimal residual disease negativity symptom score and quality of life safety and pharmacokinetics and immunogenicity.

Tecvayli is currently approved by the FDA for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy including a proteasome inhibitor an immunomodulatory agent and an anti-CD38 monoclonal antibody.

References

1. “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,” by Dr. María-Victoria Mateos. Blood.
2. “FDA approves teclistimab-cqyv for relapsed or refractory multiple myeloma,” by the U.S. Food and Drug Administration. News release; Oct. 25, 2022.

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