1. A phase I/II study of ixazomib, pomalidomide, and dexamethasone for lenalidomide and proteasome inhibitor refractory multiple myeloma (Alliance A061202).
- Author
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Voorhees PM, Suman VJ, Tuchman SA, Laubach JP, Hassoun H, Efebera YA, Mulkey F, Bova-Solem M, Santo K, Carlisle D, McCarthy PL, and Richardson PG
- Subjects
- Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Boron Compounds administration & dosage, Boron Compounds adverse effects, Dexamethasone administration & dosage, Dexamethasone adverse effects, Drug Resistance, Neoplasm drug effects, Female, Glycine administration & dosage, Glycine adverse effects, Glycine therapeutic use, Humans, Lenalidomide administration & dosage, Lenalidomide adverse effects, Male, Maximum Tolerated Dose, Middle Aged, Proteasome Inhibitors administration & dosage, Proteasome Inhibitors adverse effects, Thalidomide administration & dosage, Thalidomide adverse effects, Thalidomide therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Boron Compounds therapeutic use, Dexamethasone therapeutic use, Glycine analogs & derivatives, Lenalidomide therapeutic use, Multiple Myeloma drug therapy, Proteasome Inhibitors therapeutic use, Thalidomide analogs & derivatives
- Abstract
Preclinical studies have demonstrated activity of the oral proteasome inhibitor (PI) ixazomib (IXA) in bortezomib-resistant multiple myeloma (MM) and synergy with immunomodulatory drugs. We therefore conducted a phase I/II study to establish the safety and preliminary efficacy of IXA with pomalidomide (POM) and dexamethasone (DEX) in lenalidomide (LEN)/PI-refractory MM. Dose escalation established a 4 mg dose of POM and IXA and 20/40 mg dose of DEX as the maximum tolerated dose. The phase II portion of the trial was redesigned and started anew after six patients had been randomized to IXA-POM-DEX due to a rapidly changing treatment landscape. Among the 29 evaluable LEN/PI-refractory patients treated with IXA-POM-DEX in phase I/II, the overall response rate (partial response or better) was 51.7% with a median duration of response of 16.8 months (range 56 days to 4.1 years), median progression-free survival of 4.4 months (95% confidence interval [CI]: 3.0-18.4), and median overall survival of 34.3 months (95% CI: 19.2 to not reached). Hematologic, gastrointestinal, and constitutional adverse events were common and consistent with the side-effect profiles of the individual agents. Our results support further evaluation of this all-oral regimen in relapsed/refractory MM., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
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