Carfilzomib, Pomalidomide, and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma

Although survival rates of patients with multiple myeloma (MM) have improved over the past few years, patients inevitably relapse and become more resistant to subsequent treatments. New agents and combinations continue to be studied in an effort to identify treatment options that can extend relapse-free intervals and overall survival. Carfilzomib, a proteasome inhibitor, and pomalidomide, an immunomodulatory drug (IMiD), are both approved for the treatment of relapsed/refractory MM (RRMM). In this phase 1/2 study, researchers assessed weekly carfilzomib plus pomalidomide and low-dose dexamethasone (wKPd) for the treatment of RRMM.

The primary objective of the phase 1 trial was to determine the maximum tolerated dose of the wKPd combination, whereas the primary objective of phase 2 was to determine the rate of partial response. Patients with RRMM, who received 1 to 3 prior lines of therapy and were refractory to lenalidomide, were eligible to participate in the study.

A total of 57 patients were evaluated for this analysis. The median age was 62 years; 15 (26%) patients were considered high risk according to cytogenetic abnormalities. A total of 15 patients were enrolled in phase 1. After subsequently implementing patient safety procedures (in accordance with trial protocol) due to dose-limiting toxicities in the first 3 patients, the study proceeded, and no further dose-limiting toxicities were seen.

In phase 2, 42 patients were enrolled. The overall response rate was 64%, including 26% with at least very good partial remission. After a median follow-up of 13.6 months, the wKPd regimen demonstrated progression-free survival of 9.2 months compared with prior data of 4.5 months with pomalidomide/low-dose dexamethasone.1 Overall survival was not reached. The most frequent treatment-related grade 3 or higher adverse events (phase 1/2) were neutropenia (65%) and thrombocytopenia (13%).

Researchers concluded that the combination of weekly carfilzomib with pomalidomide and dexamethasone was highly effective in RRMM, and confirmed the efficacy of combining a proteasome inhibitor with an IMiD.

Bringhen S, et al. ASH 2016. Abstract 1145.

  1. Sanmiguel, et al. Lancet Oncol. 2013.

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