A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma.

Abstract

In this prospective, multicenter, phase 2 study, 64 patients with relapsed or relapsed and refractory multiple myeloma (MM) received up to 8 21-day cycles of bortezomib 1.0 mg/m(2) (days 1, 4, 8, and 11), lenalidomide 15 mg/day (days 1-14), and dexamethasone 40/20 mg/day (cycles 1-4) and 20/10 mg/day (cycles 5-8) (days of/after bortezomib dosing). Responding patients could receive maintenance therapy. Median age was 65 years; 66% were male, 58% had relapsed and 42% had relapsed and refractory MM, and 53%, 75%, and 6% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Forty-eight of 64 patients (75%; 90% confidence interval, 65-84) were alive without progressive disease at 6 months (primary end point). The rate of partial response or better was 64%; median duration of response was 8.7 months. Median progression-free and overall survivals were 9.5 and 30 months, respectively (median follow-up: 44 months). Common treatment-related toxicities included sensory neuropathy (53%), fatigue (50%), and neutropenia (42%); common grade 3/4 treatment-related toxicities included neutropenia (30%), thrombocytopenia (22%), and lymphopenia (11%). Grade 3 motor neuropathy was reported in 2 patients. Lenalidomide-bortezomib-dexamethasone appears effective and tolerable in patients with relapsed or relapsed and refractory MM, demonstrating substantial activity among patients with diverse prior therapies and adverse prognostic characteristics. This trial is registered with www.clinicaltrials.gov as #NCT00378209.

• Authors: Paul G Richardson, Wanling Xie, Sundar Jagannath, Andrzej Jakubowiak, Sagar Lonial, Noopur S Raje, Melissa Alsina, Irene M Ghobrial, Robert L Schlossman, Nikhil C Munshi, Amitabha Mazumder, David H Vesole, Jonathan L Kaufman, Kathleen Colson, Mary McKenney, Laura E Lunde, John Feather, Michelle E Maglio, Diane Warren, Dixil Francis, Teru Hideshima, Robert Knight, Dixie-Lee Esseltine, Constantine S Mitsiades, Edie Weller, Kenneth C Anderson
• Journal: Blood (Blood) Vol. 123 Issue 10 Pg. 1461-9 (Mar 06 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24429336 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Boronic Acids
• Pyrazines
• Thalidomide
• Bortezomib
• Dexamethasone
• Lenalidomide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Boronic Acids (administration & dosage)
• Bortezomib
• Dexamethasone (administration & dosage)
• Female
• Humans
• Lenalidomide
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, mortality, pathology)
• Neoplasm Staging
• Pyrazines (administration & dosage)
• Recurrence
• Thalidomide (administration & dosage, analogs & derivatives)
• Treatment Outcome