Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib
| Autor: | Sandra Wear, Irene M. Ghobrial, Daniel C. Sullivan, Nora Loughney, Lisa A. Nardelli, David S. Siegel, Robert L. Schlossman, Min Chen, Melissa Alsina, Paul G. Richardson, Susan L. Kelley, Palka Anand, Elizabeth Bilotti, Gail Larkins, Kenneth C. Anderson, M. Zaki, Jacob P. Laubach, Nikhil C. Munshi, Christian Jacques, Deborah Doss, Laura McBride, Rachid Baz |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Clinical Trials and Observations business.industry Bortezomib Immunology Cell Biology Hematology Neutropenia Pomalidomide medicine.disease Biochemistry Gastroenterology Surgery Thalidomide Refractory hemic and lymphatic diseases Internal medicine Medicine business Multiple myeloma Dexamethasone medicine.drug Lenalidomide |
| Zdroj: | Blood. 121:1961-1967 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | This phase 1 dose-escalation study determined the maximum tolerated dose (MTD) of oral pomalidomide (4 dose levels) administered on days 1 to 21 of each 28-day cycle in patients with relapsed and refractory multiple myeloma (RRMM). After four cycles, patients who progressed or had not achieved minimal response (serum and urine M-protein reduction of ≥ 25% and ≥ 50%) could receive dexamethasone 40 mg per week. Safety and efficacy were evaluated. Thirty-eight patients who had received both bortezomib and lenalidomide (median 6 prior therapies) were enrolled; 63% were refractory to both lenalidomide and bortezomib. There were four dose-limiting toxicities (grade 4 neutropenia) at 5 mg per day and so the MTD was 4 mg per day. Rates of peripheral neuropathy and venous thromboembolism were low (≤ 5%). Among the 38 patients enrolled (including 22 with added dexamethasone), 42% achieved minimal response or better, 21% achieved partial response or better, and 3% achieved complete response. Median duration of response, progression-free survival, and overall survival were 4.6, 4.6, and 18.3 months, respectively. Pomalidomide 4 mg per day on days 1 to 21 of each 28-day cycle, with or without dexamethasone (40 mg/week), has encouraging activity with manageable toxicity in RRMM, including those refractory to both lenalidomide and bortezomib. This study is registered at http://www.clinicaltrials.gov as #NCT00833833. |
| Databáze: | OpenAIRE |
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