A groundbreaking combination therapy involving talquetamab and teclistamab has shown promising results for patients with relapsed or refractory multiple myeloma. The treatment, however, is linked to a higher incidence of severe infections, according to a study published in the January 9 issue of the New England Journal of Medicine.

The study, led by Dr. Yael C. Cohen from Tel Aviv Sourasky Medical Center, evaluated the safety and efficacy of the dual therapy through a phase 1b-2 clinical trial. Five dose levels were tested during the initial dose-escalation phase, ultimately recommending a regimen of talquetamab at 0.8 mg/kg and teclistamab at 3.0 mg/kg every other week for phase 2. The primary focus was to assess adverse events and dose-limiting toxic effects.

In total, 94 patients participated in the trial, with 44 receiving the recommended phase 2 regimen. Patients were monitored for a median period of 20.3 months. Among them, three individuals experienced dose-limiting toxic effects, including one case of grade 4 thrombocytopenia under the recommended dose. Across all dose levels, the most common side effects were cytokine release syndrome, neutropenia, taste alterations, and nonrash skin issues.

Severe adverse events were prevalent, with 96 percent of participants experiencing grade 3 or 4 side effects, predominantly hematologic events. Notably, 64 percent of patients faced severe infections. Despite these risks, the therapy demonstrated remarkable efficacy, with 80 percent of patients responding positively to the recommended regimen and 78 percent across all dose levels. The probability of patients maintaining their response at 18 months was 86 percent with the recommended dose and 77 percent overall.

"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," the authors concluded.

The study, funded by Janssen Pharmaceuticals, the manufacturer of talquetamab and teclistamab, marks a significant step in developing advanced treatment options for challenging cases of multiple myeloma. While the high response rates are encouraging, the associated risks underscore the need for further research to optimize safety and efficacy.