Carfilzomib Weekly plus Melphalan and Prednisone in Newly Diagnosed Transplant-Ineligible Multiple Myeloma (IFM 2012-03)

Clinical Cancer Research Online First Ar.. by Leleu, X., Fouquet, G., Richez, V.,.. - 54m ago Preview

 
 
• AUTO POST
 
• SAVE TO EVERNOTE

Purpose: Carfilzomib is a novel generation proteasome inhibitor. The Carmysap trial demonstrated that twice weekly KMP (carfilzomib, melphalan, prednisone) might challenge the MPV (melphalan, prednisone, bortezomib) standard. We sought to study KMP weekly, allowing to increase carfilzomib's dose with maintained efficacy and improved safety profile. Experimental Design: IFM2012-03 is a phase 1 multicenter study of KMP weekly in newly diagnosed elderly multiple myeloma (eNDMM), aimed to determine the maximum tolerated dose (MTD) of carfilzomib. Carfilzomib was given IV at 36, 45, 56 and 70mg/m2/day on days 1,8,15,22 with melphalan and prednisone, for nine 35-days induction cycles, followed by carfilzomib maintenance for 1 year. Three dose limiting toxicities (DLT) determined MTD at the lower dose. Results: 30 eNDMM were treated, 6 per cohort at 36, 45, 56mg/m2 and 12 at 70mg/m². There was one DLT at 36mg/m2 (lymphopenia), one at 45mg/m2 (lysis syndrome), two at 56mg/m2 (cardiac insufficiency and febrile neutropenia) and two at 70mg/m2 (vomiting and elevated liver enzymes). The safety profile was acceptable, however, specific attention must be paid to the risk of cardiovascular events especially for elderly patients. The overall response rate was 93.3% with 46.6% complete response. Conclusions: The MTD dose of carfilzomib was 70mg/m2 in this KMP weekly study in eNDMM. Response rates, and especially CR rate, were remarkable in this population, and would benefit from being assessed on a larger scale study.