Marizomib Promising for Patients With Recurrent or Refractory Multiple Myeloma

Combined with low-dose dexamethasone, marizomib is active in and generally well-tolerated by heavily pretreated patients with relapsed/refractory multiple myeloma, according to a study published in Clinical Cancer Research.¹

Marizomib is an irreversible proteasome inhibitor that has demonstrated activity and specificity that is distinct from other proteasome inhibitors, such as bortezomib and carfilzomib. For the present phase 1 study researchers evaluated the maximum tolerated dose, pharmacokinetics, and pharmacodynamics of 2 dosing schedules of intravenous marizomib.

Investigators enrolled 42 patients with advanced malignancies to receive schedule A, and 44 patients with relapsed and/or refractory multiple myeloma and other hematologic malignancies to receive schedule B: schedule A consisted of marizomib 0.1 to 0.9 mg/m² over 1 to 10 minutes on days 1, 8, and 15 in 4-week cycles, while marizomib in schedule B was given at a dose of 0.075 to 0.6 mg/m² over 1 minute to 2 hours on days 1, 4, 8, and 11 in 3-week cycles.

The overall response rate was 11% among the 27 evaluable patients with relapsed and/or refractory with multiple myeloma. Responses included 1 very good partial response, 3 partial responses, 4 minimal responses, and 12 patients with stable disease.

The most common treatment-related adverse events in the schedule A group were fatigue, diarrhea, and infusion site pain, and the most frequent in the schedule B arm was fatigue.

One patient with transformed marginal zone lymphoma in the schedule A group achieved a complete response.

Reference

1. Harrison SJ, Mainwaring P, Price T, et al. Phase I clinical trial of marizomib (NPI-0052) in patients with advanced malignancies including multiple myeloma: Study NPI-0052-102 final results. Clin Cancer Res. 2016 Jul 29. doi: 10.1158/1078-0432.CCR-15-2616 [Epub ahead of print]