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A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma

Andrzej J. Jakubowiak, Dominik Dytfeld, Kent A. Griffith, Daniel Lebovic, David H. Vesole, Sundar Jagannath, Ammar Al-Zoubi, Tara Anderson, Brian Nordgren, Kristen Detweiler-Short, Keith Stockerl-Goldstein, Asra Ahmed, Terri Jobkar, Diane Durecki, Kathryn McDonnell, Melissa Mietzel, Daniel Couriel, Mark Kaminski, Ravi Vij

Abstract

This phase 1/2 study in patients with newly diagnosed multiple myeloma (N=53) assessed CRd—carfilzomib (20, 27, or 36 mg/m2, days 1, 2, 8, 9, 15, 16 and 1, 2, 15, 16 after Cycle 8), lenalidomide (25 mg/day, days 1–21), and weekly dexamethasone (40/20 mg Cycles 1–4/5+)—in 28-day cycles. After Cycle 4, transplant-eligible candidates underwent stem cell collection (SCC) then continued CRd with the option of transplantation. The maximum planned dose level (carfilzomib 36 mg/m2) was expanded in phase 2 (n=36). Thirty-five patients underwent SCC, 7 proceeded to transplantation, and the remainder resumed CRd. Grade 3/4 toxicities included hypophosphatemia (25%), hyperglycemia (23%), anemia (21%), thrombocytopenia (17%), and neutropenia (17%); peripheral neuropathy was limited to Grade 1/2 (23%). Most patients did not require dose modifications. After a median of 12 cycles (range 1–25), 62% (N=53) achieved at least near complete response (nCR) and 42% stringent CR (sCR). Responses were rapid and improved during treatment. In 36 patients completing 8 or more cycles, 78% reached at least nCR and 61% sCR. With median follow-up of 13 months (range 4–25), 24-month progression-free survival estimate was 92%. CRd was well tolerated with exceptional response rates. Registered at www.clinicaltrials.gov (#NCT01029054).

  • Submitted April 11, 2012.
  • Accepted May 12, 2012.