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

A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma

  1. David S. Siegel1,*,
  2. Thomas Martin2,
  3. Michael Wang3,
  4. Ravi Vij4,
  5. Andrzej J. Jakubowiak5,
  6. Sagar Lonial6,
  7. Suzanne Trudel7,
  8. Vishal Kukreti7,
  9. Nizar Bahlis8,
  10. Melissa Alsina9,
  11. Asher Chanan-Khan10,
  12. Francis Buadi11,
  13. Frederic J. Reu12,
  14. George Somlo13,
  15. Jeffrey Zonder14,
  16. Kevin Song15,
  17. A. Keith Stewart16,
  18. Edward Stadtmauer17,
  19. Lori Kunkel18,
  20. Sandra Wear19,
  21. Alvin F. Wong20,
  22. Robert Z. Orlowski3, and
  23. Sundar Jagannath21
  1. 1 John Theurer Cancer Center at Hackensack University, Hackensack, NJ, United States;
  2. 2 University of California, San Francisco, CA, United States;
  3. 3 MD Anderson Cancer Center, Houston, TX, United States;
  4. 4 Washington University School of Medicine, St. Louis, MO, United States;
  5. 5 University of Chicago, Chicago, IL, United States;
  6. 6 Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States;
  7. 7 University of Toronto Princess Margaret Hospital, Toronto, ON, Canada;
  8. 8 Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada;
  9. 9 H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL, United States;
  10. 10 Mayo Clinic, Jacksonville, FL, United States;
  11. 11 Mayo Clinic, Rochester, MN, United States;
  12. 12 Taussig Cancer Center - Cleveland Clinic, Cleveland, OH, United States;
  13. 13 City of Hope National Medical Center, Duarte, CA, United States;
  14. 14 Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States;
  15. 15 University of British Columbia, Vancouver, BC, Canada;
  16. 16 Mayo Clinic, Scottsdale, AZ, United States;
  17. 17 University of Pennsylvania Abramson Cancer Center, Philadelphia, PA, United States;
  18. 18 Independent Consultant, San Francisco, CA, United States;
  19. 19 Multiple Myeloma Research Consortium, Norwalk, CT, United States;
  20. 20 Onyx Pharmaceuticals, Inc., South San Francisco, CA, United States;
  21. 21 Mount Sinai Medical Center, New York, NY, United States
  1. * Corresponding author; email: dsiegel{at}


Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m2 intravenously twice weekly for 3 of 4 weeks in Cycle 1, then 27 mg/m2 for ≤12 cycles. Primary endpoint was overall response rate (ORR; ≥partial response). Secondary endpoints included clinical benefit response rate (≥minimal response), duration of response (DOR), progression-free survival, overall survival (OS), and safety. 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. ORR was 23.7% with median DOR of 7.8 months. Median OS was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). 33 patients (12.4%) experienced peripheral neuropathy, primarily Grades 1/2. Thirty-three patients (12.4%) withdrew due to an AE. Durable responses and an acceptable tolerability profile in this heavily-pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. Registered at as #NCT00511238.

  • Submitted May 2, 2012.
  • Accepted July 16, 2012.