A new myeloma therapy with the crazy name Modakafusp Alfa (previously known as TAK-573) is showing positive impact for relapsed/refractory myeloma patients who have been heavily pre-treated, including patients who are refractory to anti-CD38 monoclonal antibodies and those who have received an anti-CD38 monoclonal antibody in their most recent line of treatment. 

This drug is a completely different type of therapy called an immunocytokine. It is very similar to daratumumab and isatuximab. However, instead of being a regular antibody, it delivers interferon alpha-2b to CD38+ cells. 

Interferon is a human hormone that had been previously tried as a treatment for multiple myeloma, and it turns out that it may have been useful, but it had many side effects. The specificity of Modakafusp alfa for CD38 means that it will target the interferon directly to the myeloma cells and significantly reduce the potential side effects of the drug.

Early evaluation of Modakafusp alfa shows that it:

• Induces direct anti-proliferative effects on myeloma cells
• Stimulates an immune effect that can also attack the myeloma

Preliminary results had previously been reported from the first 59 patients in the first-in-human phase 1 trial of Modakafusp alfa in patients with relapsed/refractory multiple myeloma ( NCT03215030). Updated results from this trial were reported at ASH 2021, focusing on results from an expansion cohort with dosing every 4 weeks.

Key Findings

• Modakafusp alfa has shown promising results for the treatment of Relapsed/Refractory Multiple Myeloma of RRMM
• It has shown promising anti-myeloma activity in heavily pretreated patients
• Patients showed responses to single-agent therapy with doses starting at 0.1 mg/kg weekly
• 38% of the patients reduced their myeloma by at least 50%
• The most frequent side effects were neutropenia, leukopenia, thrombocytopenia, infections, and infusion reactions
• Median progression-free survival was 5.7 months
• Median time to response was 1.9 months
• An every four week dosing schedule of modakafusp alfa is feasible and the optimal dose and potential combinations are being explored

Hopefully, this will be a real treatment option in the future. Takeda Oncology is planning on starting the Phase II trial in the coming months.

Dan Vogl, MD of the University of Pennsylvania shares more about modakafusp alfa at the recent ASH meeting.