Blood Journal
Leading the way in experimental and clinical research in hematology

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

  1. Andrzej J. Jakubowiak1,*,
  2. Dominik Dytfeld2,
  3. Kent A. Griffith2,
  4. Daniel Lebovic2,
  5. David H. Vesole3,
  6. Sundar Jagannath4,
  7. Ammar Al-Zoubi2,
  8. Tara Anderson2,
  9. Brian Nordgren2,
  10. Kristen Detweiler-Short2,
  11. Keith Stockerl-Goldstein5,
  12. Asra Ahmed2,
  13. Terri Jobkar2,
  14. Diane Durecki2,
  15. Kathryn McDonnell1,
  16. Melissa Mietzel2,
  17. Daniel Couriel2,
  18. Mark Kaminski2, and
  19. Ravi Vij5
  1. 1 University of Chicago, Chicago, IL, United States;
  2. 2 University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, United States;
  3. 3 The John Theurer Cancer Center at Hackensack UMC, Hackensack, NJ, United States;
  4. 4 Mount Sinai Medical Center, New York, NY, United States;
  5. 5 Washington University School of Medicine, St. Louis, MO, United States
  1. * Corresponding author; email: ajakubowiak{at}medicine.bsd.uchicago.edu

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.