The Food and Drug Administration has announced the approval of teclistamab in combination with daratumumab hyaluronidase-fihj for adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. 

Today’s approval also converts the accelerated approval to traditional approval for teclistamab, as monotherapy, in adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Teclistamab received accelerated approval for this indication in 2022. 

This application is part of the FDA Commissioner’s National Priority Review Voucher (CNPV) pilot program, which is designed to accelerate the review of products with the potential to address key national priorities.

Full prescribing information for teclistamab will be posted on Drugs@FDA. 

Efficacy and safety

Efficacy was evaluated in MajesTEC-3 (NCT05083169), a randomised, open-label, multicenter trial. A total of 587 patients were randomised in the trial to the teclistamab and daratumumab hyaluronidase-fihj group (n=291) and to the investigator’s choice control group of either daratumumab hyaluronidase-fihj, pomalidomide, and dexamethasone [DPd] or daratumumab hyaluronidase-fihj, bortezomib, and dexamethasone [DVd] (n=296).

The major efficacy outcome measure was progression-free survival (PFS) by independent review committee assessment based on International Myeloma Working Group 2016 criteria.

Overall survival (OS) was an additional efficacy outcome measure. Median PFS was not reached (NR) (95% CI: NE, NE) in the teclistamab and daratumumab hyaluronidase-fihj arm and was 18.1 months (95% CI: 14.6, 22.8) in the control arm (Hazard ratio 0.17 [95% CI: 0.12, 0.23]; p-value <0.0001).

Median OS was NR (95% CI: NE, NE) and NR (95% CI: 41.4, NE) in the respective arms (Hazard ratio 0.46 [95% CI: 0.32, 0.65); p-value <0.0001).

The prescribing information for teclistamab includes a Boxed Warning for life threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS).

Teclistamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the teclistamab-Talvey REMS.

In addition to CRS, the most common side effects of teclistamab in combination with daratumumab hyaluronidase-fihj include hypogammaglobulinemia, upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and decreased weight.

See the prescribing information for the recommended doses of teclistamab and daratumumab hyaluronidase-fihj.

Source: FDA