Carfilzomib prolonged PFS in relapsed multiple myeloma
SAN FRANCISCO — The addition of carfilzomib to lenalidomide plus dexamethasone significantly extended PFS in patients with relapsed multiple myeloma who received one to three prior therapies, according to phase 3 study results presented at the ASH Annual Meeting and Exposition.
“Patients with multiple myeloma in the trial who received Kyprolis [carfilzomib] as part of their treatment stayed in remission for more than 2 years and were in complete remission three times more frequently than those patients receiving the standard of care,” A. Keith Stewart, MB.ChB., dean for research at the Mayo Clinic in Scottsdale, Ariz., told HemOnc Today. “Patients also reported a better quality of life after receiving Kyprolis, and at this interim analysis there is already a trend towards improved survival.”
The analysis included 792 patients with relapsed multiple myeloma who had received a median of two prior therapies (median age, 64 years).
Researchers randomly assigned patients 1:1 to lenalidomide (Revlimid, Celgene) plus dexamethasone with or without carfilzomib (Kyprolis, Onyx Pharmaceuticals). Patients were stratified according to their beta-2 microglobulin levels and prior treatment with bortezomib (Velcade, Millennium Pharmaceuticals; 66%) or lenalidomide (20%).
All patients received 25-mg lenalidomide on days 1 through 21 and 40-mg dexamethasone on days 1, 8, 15 and 22 of 28-day cycles. Patients assigned carfilzomib received IV infusions for 10 minutes on days 1, 2, 8, 9, 15 and 16 up to cycle 18 (days 8 and 9 were omitted after cycle 12). Carfilzomib dose increased from 20 mg/m2 on days 1 and 2 to 27 mg/m2 thereafter.
Median treatment duration was 22 cycles or 88 weeks in the carfilzomib arm and 14 cycles or 57 weeks in the lenalidomide and dexamethasone arm.
Patients who received carfilzomib achieved a median PFS of 26.3 months, which was significantly longer than the 17.6-month median PFS achieved in patients who received lenalidomide and dexamethasone alone (HR=0.69; 95% CI, 0.57-0.83).
Median OS had not yet been reached at the time of the analysis; however, researchers noted patients who received carfilzomib demonstrated a trend toward improved OS (HR=0.79; 95% CI, 0.63-0.99).
More patients who received carfilzomib were OS event-free at 24 months (73.3% vs. 65%) and demonstrated a response to treatment (87.1% vs. 66.7%). The response rate included more patients in the carfilzomib arm who achieved a stringent complete response (14.1% vs. 4.3%), complete response (17.7% vs. 5.1%) or at least a very good partial response (66.9% vs. 40.4%). Patients who received carfilzomib also exhibited a longer median response duration (28.6 months vs. 21.2 months).
Carfilzomib was significantly associated with improved Global Health Status and quality of life over 18 cycles of treatment (P=.0001).
More patients in the lenalidomide and dexamethasone arm discontinued treatment due to an adverse event (17.7% vs. 15.3%) and died during the study (8.5% vs. 7.7%).
More patients who received carfilzomib experienced grade 3 or worse neutropenia compared with patients in the other arm (29.6% vs. 26.5%), anemia (17.9% vs. 17.2%), thrombocytopenia (16.6% vs. 12.3%), pneumonia (12.5% vs. 10.5%), hypokalemia (9.4% vs. 4.9%) and hypophosphatemia (8.4% vs. 4.6%).
Any-grade diarrhea (42.3% vs. 33.7%), fatigue (32.9% vs. 30.6%), cough (28.8% vs. 17.2%), dyspnea (22.4% vs. 18%), peripheral neuropathy (17.1% vs. 17%), hypertension (14.3% vs. 6.9%), acute renal failure (8.4% vs. 7.2%), cardiac failure (6.4% vs. 4.1%) and ischemic heart disease (5.9% vs. 4.6%) occurred more frequently in the carfilzomib arm.
“Despite the fact that we added a third drug and patients were on treatment significantly longer, there was really a fairly well-balanced ratio of patients who had to discontinue treatment due to side effects,” Stewart said during a press briefing. “It’s important to note the cardiac and renal events which have been reported in some studies of heavily pretreated patients in the past, were marginally higher in the three-drug regimen, but were lower than previously reported.”
For more information:
Stewart AK. Abstract #79. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2014; San Francisco.
Disclosure: Researchers report consultant/advisory, speakers’ bureau, employment or board of director’s roles with; research funding and honoraria from; and stock ownership in Amgen, Array BioPharma, Bristol-Myers Squibb, Celgene, Genmab, Janssen, Merck, Millennium: The Takeda Oncology Company, Novartis, Onyx and Takeda.