Weekly Carfilzomib With Dexamethasone for Patients With Relapsed or Refractory M
PUBLISHED: 2015-11-30  513 total views, 2 today

James Berenson1, Roger m. Lyons2, Wael Harb3, DimitriosTzachanis4Ralph Boccia5, Robert m. Rifkin6, Priti Patel7, Jesus Berdeja8

1Department of Oncology, Institute for Myeloma and Bone Cancer Research, 2Department of Medical Oncology, US Oncology and Cancer Care Centers of South Texas, 3Department of Medical Oncology, Horizon Oncology Center, 4Department of Blood and Marrow Transplant, Cedars-Sinai Medical Center, 5Department of Medical Oncology, Center for Cancer and Blood Disorders, 6Department of Medical Oncology, US Oncology Research Inc., 7Inc., Onyx Pharmaceuticals, 8Department of Myeloma Research, Sarah Cannon Research Institute.


Objective:Carfilzomib (K) is a selective proteasomeinhibitor that is approved in the United States for the treatment of relapsedand refractory multiple myeloma. Here we present updated results fromCHAMPION-1: a multicenter, single-arm, phase 1/2 study evaluating the safetyand efficacy of weekly K with dexamethasone (DEX; Kd) in patients (pts) withrelapsed or refractory multiple myeloma (RRMM). Method: Pts who received1−3 prior regimens were eligible. In the phase 1 portion, pts received K(30-min IV infusion) on days (D) 1, 8, and 15 of a 28-day cycle in a 3+3dose-escalation scheme. All pts received K at 20mg/m2 on D1 of cycle1; subsequent dose cohorts received 45, 56, 70, or 88mg/m2successively until the maximum tolerated dose (MTD) was reached. Pts receivedDEX 40mg (IV or PO) on D1, 8, 15, and 22 of cycles 1-8; DEX was omitted on D22in cycles ≥9. In the phase 2 portion, pts are receiving K at the MTD with thesame dose and schedule for DEX. Kd is administered until progressive disease(PD) or unacceptable toxicity. Result: s are presented for pts treatedat the MTD (70mg/m2) in the phase 1 and phase 2 portions of thestudy. As of January 7, 2015, 104 pts (phase 1, n=15; phase 2, n=89 pts) wereenrolled at the MTD; the study is fully enrolled. Median pt age was 68.5 years(range, 41-88). Pts received a median of 1 prior regimen (range, 1-3).Preliminary median K treatment duration was 5.3 months (range, 0.03-18.8). Theoverall response rate (≥ partial response) was 72% (95% confidence interval[CI]: 63%-81%). Kaplan-Meier median PFS was 10.6 months (95% CI: 7.2-notestimable). The most common all-grade adverse events (AEs) were fatigue (48%),nausea (32%), and insomnia (30%). The most common grade ≥3 AEs were fatigue(9%) and thrombocytopenia, dyspnea, and back pain (6% each); 7 pts (7%)discontinued treatment due to AEs. Four pts died on study: 1 pt had sepsis,respiratory distress, pneumonia, and acute renal failure; and 1 pt each hadacute renal failure, cardiopulmonary arrest, and PD. Conclusion: At theMTD (70 mg/m2), weekly Kd is demonstrating acceptable safety andtolerability with promising efficacy in pts with RRMM.


Key Words: Carfilzomib, Multiplemyeloma

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