Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma
Paul G Richardson, Edie Weller, Sagar Lonial, Andrzej J Jakubowiak, Sundar Jagannath, Noopur S Raje, David E Avigan, Wanling Xie, Irene M Ghobrial, Robert L Schlossman, Amitabha Mazumder, Nikhil C Munshi, David H Vesole, Robin Joyce, Jonathan L Kaufman, Deborah Doss, Diane L Warren, Laura E Lunde, Sarah Kaster, Carol Delaney, Teru Hideshima, Constantine S Mitsiades, Robert Knight, Dixie-Lee Esseltine, Kenneth C Anderson, Paul G Richardson, Edie Weller, Sagar Lonial, Andrzej J Jakubowiak, Sundar Jagannath, Noopur S Raje, David E Avigan, Wanling Xie, Irene M Ghobrial, Robert L Schlossman, Amitabha Mazumder, Nikhil C Munshi, David H Vesole, Robin Joyce, Jonathan L Kaufman, Deborah Doss, Diane L Warren, Laura E Lunde, Sarah Kaster, Carol Delaney, Teru Hideshima, Constantine S Mitsiades, Robert Knight, Dixie-Lee Esseltine, Kenneth C Anderson
Abstract
This phase 1/2 study is the first prospective evaluation of lenalidomide-bortezomib-dexamethasone in front-line myeloma. Patients (N = 66) received 3-week cycles (n = 8) of bortezomib 1.0 or 1.3 mg/m(2) (days 1, 4, 8, 11), lenalidomide 15 to 25 mg (days 1-14), and dexamethasone 40 or 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). Responding patients proceeded to maintenance or transplantation. Phase 2 dosing was determined to be bortezomib 1.3 mg/m(2), lenalidomide 25 mg, and dexamethasone 20 mg. Most common toxicities included sensory neuropathy (80%) and fatigue (64%), with only 27%/2% and 32%/3% grade 2/3, respectively. In addition, 32% reported neuropathic pain (11%/3%, grade 2/3). Grade 3/4 hematologic toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6% overall), and no treatment-related mortality was observed. Rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Twenty-eight patients (42%) proceeded to undergo transplantation. With median follow-up of 21 months, estimated 18-month progression-free and overall survival for the combination treatment with/without transplantation were 75% and 97%, respectively. Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma. This study is registered at https://ichgcp.net/clinical-trials-registry/NCT00378105" title="See in ClinicalTrials.gov">NCT00378105.
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Source: PubMed