Talquetamab plus teclistamab in multiple myeloma

In a new phase 1b-2 trial recently published on The New England Journal of Medicine a combination of two bispecific antibodies, talquetamab and teclistimab, was shown to provide clinical benefits and a response in a high percentage of patients with relapsed or refractory multiple myeloma.

Talquetamab and teclistamab are two different bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class–exposed relapsed or refractory multiple myeloma. Authors investigated five dose levels of in a dose-escalation study to select a recommended phase-2 regimen and to evaluate adverse events and dose-limiting toxic effects; the trial involved 94 patients and grade 3 or 4 adverse events, most commonly hematologic events, occurred in 96% of them. At a median follow-up of 20.3 months serious infections were common and the incidence of grade 3 or 4 infections (64% across all dose levels) was higher than was seen in studies of each agent as monotherapy. A response occurred in 80% of the patients with the recommended phase 2 regimen (talquetamab 0,8 mg/kg, teclistamab 3 mg/kg every 2 weeks) and in 78% of the patients across all dose levels. «Combination therapy with teclistamab plus talquetamab showed encouraging antitumor activity in a majority of patients with relapsed or refractory multiple myeloma, with particularly deep and durable responses with the recommended phase 2 regimen. On the basis of these results, this dual- targeting, off-the-shelf combination therapy warrants further investigation in patients with relapsed or refractory multiple myeloma», authors conclude.