ASH 2014: Carfilzomib-Based Triplet Yields ‘Unprecedented’ Duration of Remission in Relapsed Myeloma
The phase III global ASPIRE trial documented an “unprecedented” duration of remission in relapsed multiple myeloma patients receiving carfilzomib (Kyprolis) plus a standard-of-care doublet, according to A. Keith Stewart, MD, of the Mayo Clinic in Scottsdale, Arizona, who presented the results at a press briefing during the 56th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 79).
A median progression-free survival of 26.3 months was achieved for patients who received carfilzomib plus lenalidomide (Revlimid) and low-dose dexamethasone, while the control arm, who received lenalidomide/dexamethasone alone, had a median progression-free survival of 17.6 months, a 31% reduction in risk (P < .0001), Dr. Stewart reported.
ASPIRE Trial
ASPIRE enrolled 792 relapsed or refractory patients from 20 countries. Patients had received one to three prior regimens (on average, two).
“By adding carfilzomib to the gold standard in multiple myeloma therapy, we are observing an unprecedented duration of remission, without additional toxicity, in relapsed and heavily pretreated patients,” Dr. Stewart said.
“The best result ever reported in this population,” he said, was a median progression-free survival of just 19 months, which was achieved with bortezomib (Velcade) plus lenalidomide/dexamethasone. “We have never seen this duration of remission with this side effect profile,” he said at the briefing.
The objective response rate was also significantly higher for the triplet, 87% vs 67%. “Even more impressively,” he added, “the rate of complete responses was more than three times higher for the three drugs, 32% vs 9% (P < .0001).”
At the time of this interim analysis, median overall survival was not reached in either group, but there was a trend toward longer survival in the carfilzomib arm. At 24 months, overall survival event-free rates were 73.3% and 65.0%, respectively; median duration of response was 28.6 and 21.2 months, respectively, Dr. Stewart reported.
No Increase in Side Effects
Despite the addition of carfilzomib, toxicity was not significantly increased in that arm. Patients receiving the triplet actually had higher health-related quality of-life scores, he reported.
Treatment discontinuations due to study drug were similar between the arms, approximately 16%. Rates of peripheral neuropathy were also the same, 17%. Cardiac and renal events, which have been reported in some previous studies of heavily pretreated patients, were “marginally higher” in the three-drug regimen but overall consistent or even lower than those previously reported, he said.
“Despite adding a third drug and being on treatment significantly longer,” Dr. Stewart noted, patients tolerated the triplet well and remained on treatment. The regimen represents a potential new standard of care, according to Dr. Stewart.
Dr. Stewart is a consultant for Novartis, Array BioPharma, Bristol-Myers Squibb, and Celgene, and receives research funding from Millennium. For full disclosures of the study authors, view the study abstract.
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