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

Abstract

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/m(2) intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m(2) for ≤ 12 cycles. The primary endpoint was overall response rate (≥ partial response). Secondary endpoints included clinical benefit response rate (≥ minimal response), duration of response, progression-free survival, overall survival, and safety. A total of 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. Overall response rate was 23.7% with median duration of response of 7.8 months. Median overall survival was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirty-three patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) withdrew because of an AE. Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. This trial was registered at www.clinicaltrials.gov as #NCT00511238.

• Authors: David S Siegel, Thomas Martin, Michael Wang, Ravi Vij, Andrzej J Jakubowiak, Sagar Lonial, Suzanne Trudel, Vishal Kukreti, Nizar Bahlis, Melissa Alsina, Asher Chanan-Khan, Francis Buadi, Frederic J Reu, George Somlo, Jeffrey Zonder, Kevin Song, A Keith Stewart, Edward Stadtmauer, Lori Kunkel, Sandra Wear, Alvin F Wong, Robert Z Orlowski, Sundar Jagannath
• Journal: Blood (Blood) Vol. 120 Issue 14 Pg. 2817-25 (Oct 04 2012) ISSN: 1528-0020 [Electronic] United States
• PMID: 22833546 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Oligopeptides
• carfilzomib

Topics

• Adult
• Aged
• Aged, 80 and over
• Drug Resistance, Neoplasm
• Female
• Humans
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, mortality)
• Neoplasm Recurrence, Local (drug therapy, mortality)
• Neoplasm Staging
• Oligopeptides (therapeutic use)
• Pilot Projects
• Prognosis
• Salvage Therapy
• Survival Rate