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- Title
Oprozomib, pomalidomide, and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma.
- Authors
Shah, Jatin; Usmani, Saad; Stadtmauer, Edward A.; Rifkin, Robert M.; Berenson, James R.; Berdeja, Jesus G.; Lyons, Roger M.; Klippel, Zandra; Chang, Yu-Lin; Niesvizky, Ruben
- Abstract
<bold>Introduction: </bold>This phase Ib study evaluated oprozomib, an oral proteasome inhibitor, plus pomalidomide-dexamethasone in relapsed/refractory multiple myeloma (RRMM).<bold>Patients and Methods: </bold>Patients received oprozomib once-daily on days 1 to 5 and 15 to 19 (5/14 schedule; 150 mg/day starting dose) or on 2 consecutive days weekly (2/7 schedule; 210 mg/day starting dose) of 28-day cycles, pomalidomide on days 1 to 21 (4 mg/day starting dose), and dexamethasone 20 mg on 2 consecutive days weekly. A 3 + 3 dose-escalation schema was used to determine the maximum tolerated dose.<bold>Results: </bold>Thirty-one patients were treated (5/14, n = 4; 2/7, n = 27). Oprozomib maximum tolerated dose was not defined. The 2/7 schedule (oprozomib 210 mg/day, pomalidomide 4 mg/day) was selected for dose expansion based on overall safety (n = 17). In this group, the most common adverse events (AEs) were gastrointestinal (diarrhea [88.2%], nausea [58.8%], and vomiting [58.8%]); grade ≥ 3 gastrointestinal AEs were uncommon. The most common grade ≥ 3 AEs were hematologic (anemia [47.1%], neutropenia [35.3%], and thrombocytopenia [29.4%]). One dose-limiting toxicity (gastric hemorrhage) occurred; 3 patients discontinued owing to AEs. The overall response rate was 70.6%.<bold>Conclusion: </bold>Safety and pharmacokinetic profiles were concerns with the oprozomib formulation used in this study and need to be improved. Oprozomib-pomalidomide-dexamethasone (2/7 schedule) had encouraging efficacy, supporting an ongoing phase Ib study evaluating new oprozomib formulations for this combination in relapsed/refractory multiple myeloma.
- Publication
Clinical Lymphoma, Myeloma & Leukemia, 2019, Vol 19, Issue 9, p570
- ISSN
2152-2650
- Publication type
journal article
- DOI
10.1016/j.clml.2019.05.017