Targeted interferon therapy with modakafusp alfa for relapsed or refractory multiple myeloma

Area of Science:

• Oncology
• Immunotherapy
• Hematology

Background:

• Interferon alfa exhibits activity against multiple myeloma (MM).
• Modakafusp alfa is an innovative immunocytokine designed for targeted delivery of interferon alfa to CD38-expressing cells.
• Patients with relapsed/refractory MM often have limited treatment options after failure of standard therapies.

Purpose of the Study:

• To evaluate the safety and efficacy of modakafusp alfa in patients with relapsed/refractory multiple myeloma.
• To determine the maximum tolerated dose (MTD) and optimal dosing schedule for modakafusp alfa.
• To assess the immunomodulatory effects and antitumor activity of modakafusp alfa.

Main Methods:

• A phase 1/2 trial involving 106 patients with relapsed/refractory multiple myeloma, many refractory to prior anti-CD38 antibody therapy.
• Dose escalation identified the maximum tolerated dose (MTD) and feasible schedule (1.5 mg/kg every 4 weeks).
• Overall response rate (ORR), duration of response, progression-free survival, and adverse events were assessed.

Main Results:

• The maximum tolerated dose was determined to be 3 mg/kg, with 1.5 mg/kg every 4 weeks identified as the most feasible schedule.
• In 30 patients treated at 1.5 mg/kg every 4 weeks, the ORR was 43.3%, with a median duration of response of 15.1 months.
• Hematologic adverse events, primarily neutropenia and thrombocytopenia, were common. Modakafusp alfa induced immune activation and upregulation of type 1 interferon gene signature.

Conclusions:

• Modakafusp alfa demonstrates significant antitumor activity and immune activation in heavily pretreated patients with relapsed/refractory multiple myeloma.
• The immunocytokine is generally well-tolerated, with manageable hematologic toxicities.
• Modakafusp alfa represents a promising therapeutic option for patients with multiple myeloma who have exhausted other treatment avenues.