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Carfilzomib combination highly effective in older patients with myeloma
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Carfilzomib in combination with cyclophosphamide and dexamethasone induced high rates of complete response in older patients with newly diagnosed multiple myeloma, according to results of a randomized, multicenter, open-label phase 2 study.
The regimen also exhibited a good safety profile, researchers wrote.
Sara Bringhen, MD, of the myeloma unit in the division of hematology at Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino in Italy, and colleagues assessed the safety and efficacy of carfilzomib (Kyprolis, Onyx Pharmaceuticals) — novel and irreversible proteasome inhibitor — in combination with cyclophosphamide and dexamethasone in patients with newly diagnosed multiple myeloma.
All 58 patients were aged ≥65 years and were ineligible for autologous stem cell transplantation.
Nineteen patients were enrolled in the first stage of the trial. After researchers determined the optimal dose, 34 additional patients were enrolled in the trial’s second stage.
Treatment — administered for up to nine 28-day cycles — consisted of 300 mg/m2 oral cyclophosphamide on days 1, 8 and 15; 40 mg oral dexamethasone on days 1, 8, 15 and 22; and 30-minute infusions of IV carfilzomib on days 1, 2, 8, 9, 15 and 16. Carfilzomib doses were 20 mg/m2 on days 1 and 2 of the first cycle, then 36 mg/m2 thereafter.
All patients received maintenance carfilzomib until disease progression or treatment intolerance.
Evaluation of toxicity and efficacy at the end of the third cycle served as the primary outcome measure. Secondary outcome measures included response rates, PFS, OS, time to progression, duration of response and time to next therapy.
Patients underwent a median nine induction cycles (range, 1-9). Ninety-five percent of patients achieved at least a partial response. Researchers reported at least a very good partial response in 71% of patients, at least a near complete response in 49% of patients, and stringent complete response in 20% of patients.
Researchers reported a 2-year PFS rate of 76% and a 2-year OS rate of 87%.
Fourteen percent of patients discontinued treatment due to adverse events, and 21% required carfilzomib dose reductions. The most common grade 3 to grade 5 adverse events included neutropenia (20%), anemia (11%) and cardiopulmonary adverse events (7%).
“This is the first study of carfilzomib in combination with an alkylating agent in elderly patients with newly diagnosed multiple myeloma; results showed high complete response rates and a good safety profile,” the researchers wrote.
Disclosure: The researchers report honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Millennium, Novartis and Onyx; advisory board roles with Bristol-Myers Squibb, Celgene, Janssen-Cilag, Millennium, Merck Sharp & Dohme and Onyx; consultant fees from Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilag, Janssen, Millennium and Onyx; and research support from Celgene, Janssen, Janssen-Cilag and Millennium.
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