Marizomib, a novel, irreversible proteasome inhibitor distinct from bortezomib and carfilzomib, was generally well tolerated and may have clinical activity in previously treated, relapsed or refractory multiple myeloma, a study published in the journal Blood has shown.1

For the phase 1 portion of this study, researchers sought to determine a maximum tolerated dose and recommended phase 2 dose.

Researchers enrolled 68 patients with relapsed/refractory multiple myeloma and assigned 32 to receive marizomib 0.025–0.7 mg/m2 IV once weekly on days 1, 8, 15 of 4-week cycles (schedule A) or 0.15–0.6 mg/m2 twice weekly on days 1, 4, 8, 11 of 3-week cycles schedule B). Patients in the schedule B group were eligible to receive concomitant dexamethasone, as well.

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Researchers ultimately determined that 0.7 mg/m2 infused over 10 minutes and 0.5 mg/m2 infused over 2 hours would be the recommended phase 2 doses for schedule A and B, respectively.

On average, patients in the schedule A group had received approximately 5 prior treatment regimens and those in the schedule B group had received about 7 prior regimens.

Results showed the most frequently reported treatment-related adverse events were fatigue, headache, nausea, diarrhea, dizziness, and vomiting.

In terms of efficacy, 6 patients achieved a clinical benefit response. Of those, 5 had partial responses: 1 patient receiving schedule A and 4 on schedule B. Three of the 4 on schedule B were receiving concomitant dexamethasone. Further, these responses were in patients who had received prior bortezomib, lenalidomide, and/or thalidomide.

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The findings suggest activity of marizomib in this heavily treated population with a minimal number of dose-limiting toxicities. Studies evaluating marizomib in combination with pomalidomide and dexamethasone are currently underway.


  1. Richardson PG, Zimmerman TM, Hofmeister CC, et al. Phase 1 study of marizomib in relapsed or relapsed and refractory multiple myeloma; NPI 0052 101 Part 1 [published online ahead of print March 23, 2016]. Blood. doi: 10.1182/blood-2015-12-686378.