A recent phase 2 randomized study published in Blood found that modakafusp alfa, a novel immunocytokine, exhibited significant antitumor activity as a monotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Modakafusp alfa, a fusion of an anti-CD38 monoclonal antibody (mAb) with two attenuated interferon-α2 cytokines, may enhance immune activation against myeloma cells while minimizing toxicity.
The global, multicenter, open-label, randomized study enrolled adult patients with RRMM who had received at least three prior lines of therapy and were refractory to anti-CD38 monoclonal antibodies. A total of 147 patients were randomized into two arms and received either 120 or 240 mg every 4 weeks until unacceptable toxicity, patient withdrawal, or disease progression. The primary endpoint was overall response rate (ORR), with secondary endpoints including progression-free survival (PFS), duration of response (DOR), and safety profile.
At data cutoff, 17 patients in each arm were still receiving ongoing treatment. Of the 112 patients that discontinued treatment, 73 between both arms discontinued due to progressive disease. The ORR was 32% (95% CI, 21.8-44.6) in the 120-mg arm, and 41% (95% CI, 30.1-53.3) in the 240-mg arm, with 27 and 36 patients having at least minimal response, respectively. PFS was 4.1 months and 5.3 months, respectively, and median DOR was only reached in the 240 mg arm at 9.2 months.
“We hypothesize that both T-cell–redirecting therapies and anti-CD38 mAbs may be appropriate for further investigation,” said Sarah A. Holstein, MD, PhD, of the Department of Internal Medicine, University of Nebraska Medical Center in Omaha.
The most common adverse events included thrombocytopenia, neutropenia, and anemia, which were generally manageable and consistent with the known profile of interferon-based therapies. No new safety signals were identified.
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