Weekly carfilzomib,lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study |
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| Authors: | Noa Biran David Siegel Jesus G. Berdeja Noopur Raje Robert Frank Cornell Melissa Alsina Tibor Kovacsovics Belle Fang Amy S. Kimball Ola Landgren |
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| Affiliation: | 1. Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey;2. Department of Medicine, Sarah Cannon Research Institute, Nashville, Tennessee;3. Department of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts;4. Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee;5. Department of Blood and Marrow Transplantation, Moffit Cancer Center, Tampa, Florida;6. Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah;7. Global Biostatistical Science, Amgen Inc., Thousand Oaks, California;8. Global Development, Amgen Inc., Thousand Oaks, California;9. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York |
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| Abstract: | Twice-weekly carfilzomib (27 mg/m2) with lenalidomide-dexamethasone (KRd) is a standard-of-care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once-weekly carfilzomib in RRMM. Patients received carfilzomib (30-minute infusion; 56 or 70mg/m2) on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28-day cycles. Primary objective was safety/tolerability; efficacy was a secondary objective. Fifty-six RRMM patients enrolled: 22 during dose evaluation (56-mg/m2, n = 10; 70-mg/m2, n = 12) and 34 during dose expansion (all initiated dosing at 70 mg/m2). After 2 fatal adverse events (AEs) during 70-mg/m2 dose expansion, dosage reduction to 56 mg/m2 was permitted. Results are presented for carfilzomib 56-mg/m2 (n = 10) and 70-mg/m2 groups (dose evaluation/expansion; n = 46). Median carfilzomib dose was 53.2 mg/m2 (56-mg/m2 group) and 62.4 mg/m2 (70-mg/m2 group). Grade ≥3 AE rates were 70.0% (56 mg/m2) and 69.6% (70 mg/m2). Overall response rates were 90.0% (56 mg/m2) and 89.1% (70 mg/m2); ≥very good partial response rates were 50.0% (56 mg/m2) and 73.9% (70 mg/m2). Once-weekly KRd was active with acceptable toxicity in RRMM, supporting further evaluation of this regimen. |
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