Three Drugs Top Two in Relapsed Multiple Myeloma

Patients with relapsed multiple myeloma had a 9-month improvement in progression-free survival (PFS) when they received the proteasome inhibitor carfilzomib (Kyprolis) in addition to standard therapy, a randomized trial showed.

The addition of carfilzomib to lenalidomide (Revlimid) and dexamethasone was associated with a median PFS of 26.3 months compared with 17.6 months for lenalidomide and dexamethasone. Median overall survival (OS) has yet to be reached in either group, but preliminary data suggest an advantage for the carfilzomib group, reported A. Keith Stewart, MB ChB, of the Mayo Clinic in Scottsdale, Ariz., at the American Society of Hematology (ASH) meeting.

"The primary endpoint of progression-free survival was met, with an unprecedented median time of 26 months," Stewart said during an ASH press briefing. "There was a trend toward an overall survival benefit, but that has not yet been confirmed."

In response to a question about his use of the term "unprecedented," Stewart said, "In this same population of patients - patients who have relapsed one, two, or three times - the best result ever reported before with any combination chemotherapy was about 19 months."

The results were published simultaneously in the New England Journal of Medicine.

Although therapeutic advancements have substantially improved survival in myeloma, relapse remains an ongoing risk, necessitating continued evaluation of new and novel therapeutic approaches. The combination of lenalidomide and high-dose dexamethasone received FDA approval for relapsed multiple myeloma after phase III trials demonstrated superiority to dexamethasone alone, including a median PFS of 11.1 months.

Carfilzomib has an approved indication as monotherapy for relapsed myeloma. Preliminary clinical trials showed that the combination of carfilzomib, lenalidomide, and weekly dexamethasone was active in relapsed myeloma and had a side-effect profile consistent with the drugs' known toxicity. The results set the stage for the randomized phase III ASPIRE trial.

Patients with relapsed myeloma and a treatment history of no more than three prior regimens were eligible for the trial. Prior treatment with bortezomib (Velcade) or with lenalidomide-dexamethasone combination therapy did not automatically disqualify patients.

Investigators in North America, Europe, and the Middle East randomized 792 patients to receive lenalidomide and dexamethasone alone or in combination with carfilzomib. The trial had a primary endpoint of PFS, and secondary endpoints consisted of OS, overall response rate, duration of response, health-related quality of life, and safety.

The trial ended early after an interim analysis showed that the carfilzomib arm had met the primary endpoint. At the data cutoff, 29.8% of the carfilzomib group and 21.7% of the control group remained on therapy.