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Effect of CMP, carfilzomib (CFZ) plus melphalan-prednisone (MP), on response rates in elderly patients (pts) with newly diagnosed multiple myeloma (NDMM): Results of a phase (Ph) I/II trial.
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Background: MP+thalidomide (MPT) and MP+bortezomib (MPV) have shown significant progression-free survival and overall survival (OS) benefits in NDMM pts > 65 years (y) but are associated with peripheral neuropathy (PN). CFZ, a novel proteasome inhibitor, has shown promising activity and a favorable toxicity profile with low PN rates. Methods: This PhI/II study in NDMM >65y was designed to determine maximum tolerated dose (MTD) of CMP and assess safety and efficacy. In PhI, CFZ was started at 20mg/m2, then escalated to 27, 36, and 45mg/m2, given IV in 42-day (D) cycles (C) on D1/2/8/9/22/23/29/30 for 9C. Melphalan 9mg/m² and prednisone 60mg/m² were given PO D1–4 of every 45-day cycle. MTD was based on dose-limiting toxicity (DLT) in C1 defined as any grade (G) 4 hematologic adverse event (AE), any hematologic AE preventing aministration of ≥ 2 C1 CFZ doses except G4 thrombocytopenia without bleeding or G4 neutropenia ≤7D, ≥G3 febrile neutropenia, or any ≥G3 nonhematologic AE. Results: As of Jan 6, 2013, 24 pts have been enrolled in PhI: 6 for each dose level. There were 2 DLTs at 45mg/m2(fever, hypotension) resulting in a MTD of 36mg/m². In PhII, 45 additional pts received CMP at 36mg/m² CFZ for N=69 total PhI/II pts (median age 74y). ORR was 89% with 51% ≥VGPR. With median follow-up of 12 mo, the projected 2y OS was 89.9%. CMP was well tolerated without PN ≥G2. Conclusions: These results compare favorably to those of MPV, MPT, MP+lenalidomide (R), and R+dex in similar pts (ORR 71% San Miguel NEnglJMed2008, 76% Facon Lancet2007, 80% Palumbo JClinOncol2007 and 85% Rajkumar LancetOncol2010, respectively). CFZ 36mg/m2 +MP is tolerable and effective in elderly NDMM pts. Treatment is ongoing. Final safety and efficacy data will be presented during the meeting. Clinical trial information: NCT01279694.