Session: 653. Myeloma - Therapy, excluding Transplantation: Clinical issues in myeloma and amyloidosis patients: novel agent and novel agent-based combinations
Methods: CFZ was given as a 30-minute IV infusion on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Cycle1 Day1–2 doses were 20 mg/m2, followed by escalation to 56mg/m2. Dexamethasone 8 mg was given prior to infusion as premedication to mitigate infusion-related reactions. Patients who did not achieve a partial response (PR) after two cycles of CFZ or initially responded to single agent CFZ, but later showed evidence of progression of disease (POD) had dexamethasone (40mg/week) added to their regimen. Overall response rate (ORR; [sCR + CR + VGPR + PR]) was determined according to International Myeloma Working Group Uniform Response Criteria. Subjects were evaluated for adverse events according to the Common Terminology Criteria for Adverse Events v 4.0.
Results: Thirty-four patients have been enrolled. Patients had received a median of 5 (range 1-11) prior treatment regimens and included 7 patients who relapsed following allogeneic stem cell transplant. Seventy eight percent of patients were bortezomib-refractory. ORR among patients who completed 4 cycles of therapy or experienced POD prior to completing 4 cycles of therapy was 58% with 1 CR, 7 VGPRs, and 6 PRs. ORR after 4 cycles of therapy was 57% in bortezomib-refractory patients. By intention to treat analysis the ORR in all comers was 50%. Median progression free survival was 4.6 months, median overall survival has not been reached with a median follow-up among survivors of 9.6 months (range: 0.3-14.3 months). The average time to best response was two cycles. Three out of the 11 patients that had dexamethasone 40mg/week added to their regimen obtained an improved response. Twelve patients (35%) were dose reduced. Treatment emergent, non-hematologic Grade 3/4 adverse events for which contribution of CFZ cannot be excluded were: HTN (n = 7), lung infection (n = 6), pulmonary edema (n = 3), reduced ejection fraction (n=1), sepsis (n=2), febrile neutropenia (n=1), bacteremia (n = 1), protothecosis (n = 1), fatigue (n=1), neuropathy (n=1), microangiopathic hemolytic anemia(n=1), nausea/vomiting/+/- diarrhea (n = 2), gastrointestinal bleed in the setting of Grade 4 thrombocytopenia (n = 1), hyperkalemia (n = 1).
Conclusions: The 20/56 mg/m2 dose for CFZ administered as a 30-minute IV infusion was associated with 58% ORR, in a heavily pretreated patient population, including 21% of patients w/ prior allogeneic transplant, where the majority of patients were bortezomib-refractory. The ORR from this study is consistent with the one previously reported at the similar dose. Higher doses of carfilzomib continue to be explored in ongoing Phase 2 and Phase 3 studies.
Disclosures: Landau: Onyx: Research Funding; Milleneum: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Hassoun: Millenium: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Giralt: Onyx: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Milleneum: Membership on an entity’s Board of Directors or advisory committees.
See more of: Oral and Poster Abstracts
*signifies non-member of ASH