FDA Approves Teclistamab/Daratumumab Combo in R/R Multiple Myeloma

The FDA approved the combination of teclistamab-cqyv (Tecvayli) plus daratumumab and hyaluronidase-fihj (Darzalex Faspro) in patients with relapsed/refractory multiple myeloma (R/R MM) following 1 or more prior lines of treatment including a proteasome inhibitor and lenalidomide (Revlimid).¹

The rapid approval came via the Commissioner’s National Priority Voucher (CNPV) Pilot Program based on the strong progression-free survival (PFS) and overall survival (OS) results in this population from the phase 3 MajesTEC-3 trial (NCT05083169).

The FDA also converted the existing accelerated approval for teclistamab after 4 prior lines of therapy including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody to full approval.

Dramatic Results From MajesTEC-3

In the randomized trial of 587 patients with R/R MM at a median of 34.5 months’ follow-up, treatment with the combination resulted in an 83% reduction in the risk of progression or death compared with standard-of-care (SOC) treatment (HR, 0.17; 95% CI, 0.12-0.23; P < .0001).² The 36-month PFS rates were 83.4% and 29.7%, respectively. The respective 36-month OS rates were 83.3% and 65.0%, and OS data showed a favorable trend toward teclistamab/daratumumab across all prespecified subgroups.

Teclistamab/daratumumab was also more likely to result in a complete response (OR, 9.56; 95% CI, 6.47-14.14), overall response (OR, 2.65; 95% CI, 1.68-4.18), and minimal residual disease (MRD) negativity (OR, 6.78; 95% CI, 4.53-10.15) compared with those treated with SOC.

National Priority Voucher Program

The Commissioner’s National Priority Voucher was awarded to teclistamab/daratumumab on December 15, 2025, shortly after the phase 3 clinical trial data were released in November.³ The Priority Voucher pilot program accelerates the FDA’s review process for drugs that meet certain criteria such as addressing a public health crisis or a large unmet medical need. Recipients receive enhanced communications with review staff and review decisions are made within 1 to 2 months following submission of an application.

About the MajesTEC-3 Trial

MajesTEC-3 is a global, randomized study evaluating the efficacy and safety of the bispecific antibody teclistamab in combination with the anti-CD38 monoclonal antibody daratumumab vs investigator’s choice of daratumumab, pomalidomide (Pomalyst), and dexamethasone or daratumumab, bortezomib (Velcade), and dexamethasone in patients with R/R MM who have received 1 to 3 prior lines of therapy. Patients were randomly assigned to receive either teclistamab/daratumumab (n = 291) or SOC (n = 296).²

Teclistamab was given with a dose of 1.5 mg/kg weekly in cycle 1 following 2 step-up doses of 0.06 and 0.3 mg/kg, 1.5 mg/kg weekly in cycle 2, 3 mg/kg every 2 weeks from cycles 3 to 6, and 3 mg/kg every 4 weeks from cycle 7 and onward. The teclistamab schedule aligned with the administration of subcutaneous daratumumab at the approved dose.

Infection prophylaxis including intravenous immunoglobulin (IVIG) was administered according to institutional guidelines and a protocol amendment affirmed the importance of monitoring immunoglobulin G levels and protocol-specified supplementation guidance.

Safety of Combination Therapy

No new adverse events (AE) were noted compared with those of the individual agents. Cytokine release syndrome (CRS) occurred at a lower rate than with teclistamab monotherapy in the MajesTEC-1 trial and was primarily grade 1 during the step-up dosing. Investigators noted that prophylactic tocilizumab (Actemra) is now recommended to reduce the incidence and severity of CRS but was not given in the trial.

Over 95% of patients had an AE of grade 3 or 4 in both arms. Neutropenia was the most common high-grade AE, occurring at a rate of 75.6% in the experimental group and 78.6% in the SOC group. Other AEs of concern included infectious complications such as grade 3 or 4 pneumonia, which occurred at a 16.6% and 14.8% in the respective arms. The trial took place during the COVID-19 pandemic before the adoption of guidelines for infection prevention with these therapies. COVID-19 pneumonia of grade 3 or 4 occurred in 11.3% in the experimental group vs 2.4% in the control arm.

A total of 7.1% of patients receiving teclistamab/daratumumab died of AEs during the trial, primarily cytopenias and infections. Investigators stated that the infection prevention protocols and use of IVIG according to guidelines, as well as the monthly dosing schedule after 6 months, could reduce high-grade infections.

The approval of the combination marks the earliest indication for a bispecific antibody in multiple myeloma. Another trial, MajesTEC-9 (NCT05572515), reported positive outcomes with teclistamab as monotherapy in patients who have received prior anti-CD38 antibody therapy.

REFERENCES

1. FDA approves teclistamab in combination with daratumumab hyaluronidase-fihj for relapsed or refractory multiple myeloma. News release. US FDA. March 5, 2026. https://tinyurl.com/mry968za

2. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. Published online December 9, 2025. doi:10.1056/NEJMoa2514663

3. FDA proactively awards National Priority Voucher based on strong phase 3 study results. News release. FDA. December 15, 2025. Accessed January 21, 2026. https://tinyurl.com/b9d3ewat