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Carfilzomib-based therapy extends OS in relapsed, refractory multiple myeloma
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The addition of carfilzomib to lenalidomide and dexamethasone reduced risk for death by 21% among patients with relapsed or refractory multiple myeloma, according to results from the ASPIRE trial.
“This study provides further evidence that carfilzomib-based regimens are among the most potent in our multiple myeloma armamentarium,” David S. Siegel, MD, PhD, chief of the division of multiple myeloma at John Theurer Cancer Center, told HemOnc Today. “Carfilzomib continues to be underutilized for a number of complex reasons related to perceived toxicities and logistical concerns.”
The phase 3 ASPIRE trial included 792 patients from North America, Europe and Israel who had received one to three prior lines of therapy for relapsed multiple myeloma.
Researchers randomly assigned patients 1:1 to lenalidomide (Revlimid, Celgene) and dexamethasone with or without the proteasome inhibitor carfilzomib (Kyprolis, Amgen).
Investigators administered carfilzomib via infusion on days 1,2, 8, 9, 15 and 16 during cycles one to 12, then on days 1, 2, 15 and 16 in cycles 13 to 18. Lenalidomide was administered on days 1 to 21, and dexamethasone was administered on days 1, 8, 15 and 22.
Treatment continued in 28-day cycles until consent withdrawal, disease progression or unacceptable toxicity.
Protocol dictated that carfilzomib end after 18 cycles due to limited long-term safety data available at the time of trial initiation.
Results from an interim analysis showed the addition of carfilzomib to lenalidomide and dexamethasone improved PFS (HR = 0.69; 95% CI, 0.57-0.83). Overall response, complete response and median duration of response rates also improved.
Median follow-up for OS was 67.1 months. At data cutoff, 129 patients (32.6%) who received carfilzomib, lenalidomide and dexamethasone and 98 patients (24.7%) who received lenalidomide and dexamethasone remained alive.
Patients who received carfilzomib achieved longer median OS (48.3 months vs. 40.4 months; HR = 0.79; 95% CI, 0.67-0.95).
Researchers observed the OS benefit with carfilzomib among patients who had received one prior line of therapy (median, 47.3 months vs. 35.9 months; HR = 0.81; 95% CI, 0.62-1.06), as well as those who had received two prior lines of therapy (median, 48.8 months vs. 42.3 months; HR = 0.79; 95% CI, 0.62-0.99).
The most common adverse events among carfilzomib-treated patients included diarrhea (44.4%), anemia (43.1%), neutropenia (40.1%), fatigue (33.4%), upper respiratory tract infection (30.1%), pyrexia (29.8%), cough (29.6%), hypokalemia (29.6%), thrombocytopenia (29.3%), muscle spasms (27%), pneumonia (23.2%), nausea (20.9%), constipation (20.7%), insomnia (20.7%), viral upper respiratory tract infection (20.4%) and bronchitis 20.2%).
Grade 3 adverse events that occurred more frequently in the carfilzomib group included acute renal failure (3.8% vs. 3.3%), cardiac failure (4.3% vs. 2.1%), ischemic heart disease (3.8% vs. 2.3%), hypertension (6.4% vs. 2.3%) and hematopoietic thrombocytopenia (20.2% vs. 14.9%).
“I hope that this study will go some way to reassure both hematologists/oncologists and patients that this agent is too active and too well-tolerated to be avoided,” Siegel said. – by Melinda Stevens
For more information:
David S. Siegel, MD, PhD, can be reached at John Theurer Cancer Center, Hackensack University Medical Center, 92 Second St., Third floor, Hackensack, NJ; e-mail: davids.siegel@hackensackmeridian.org.
Disclosures: Siegel reports speaker bureau roles with Amgen, Bristol-Myers Squibb, Celgene, Janssen Oncology and Takeda Pharmaceuticals. Please see the study for a list of all other authors’ relevant financial disclosures.
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