SAN FRANCISCO—Patients with treatment-naïve multiple myeloma who received once-weekly carfilzomib with cyclophosphamide and dexamethasone had improved responses over time.

The study (Abstract 175) was the first prospective study to evaluate this dosing interval in this population and was presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.

“The response rate observed with weekly carfilzomib compares favorably with similar studies with standard twice-weekly carfilzomib infusion,” said Antonio Palumbo, MD, of the Myeloma Unit, Division of Hematology at the University of Torino in Torino, Italy.

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The phase 1/2 study enrolled 30 patients with symptomatic newly diagnosed multiple myeloma who were 65 years of age or older or ineligible for autologous stem cell transplantation.

Oral cyclophosphamide was administered at 300 mg/m2 on days 1, 8, 15 and oral dexamethasone at 40 mg on days 1, 8, 15, 22 for all carfilzomib dose levels as induction for cycles 1 to 9; patients then received carfilzomib maintenance until disease progression.

In the phase 1 portion of the study, 12 patients received carfilzomib at 45 mg/m2 (3 patients), 6 at 56 mg/m2 (1 dose-limiting toxicity, creatinine increase, occurred), and 3 at 70 mg/m2.

The maximum tolerated dose (MTD) of weekly carfilzomib was established at 70 mg/m2, and an additional 18 patients were treated at this dose.

Median age was 74 years (range, 64-79); 30% were older than 75 years.

Preliminary response data in the 28 patients evaluable for response (1 discontinued due to pulmonary edema and 1 is ongoing in the first cycle) revealed that median time to first response was 1 month. The median duration of response was not reached.

After a median of 8 cycles (range, 1-9), 86% achieved at least a partial response (PR); 64%, at least a very good partial response; and 25%, a stringent complete response (CR), CR, or near CR. Responses improved over time; after 9 cycles, 99% had a PR, 91% had at least a very good PR, and 41%, at least a near CR.

A total of 5 patients had a serious adverse event (AE) and 4 had a drug-related serious AE. Three patients had a dose reduction due to an AE and there was 1 on-study death.

Grade 3 or 4 hematologic AEs occurred in 23% of patients at the once-weekly carfilzomib dose compared with 27% at the twice-weekly dose. Grade 3 or 4 nonhematologic AEs occurred in 30% and 29% of patients, respectively. Grade 3 anemia, neutropenia, and thrombocytopenia were observed, as was grade 4 cardiac and pulmonary embolism.

Three patients required carfilzomib dose reduction and 7 patients discontinued treatment, 3 due to AEs, 2 due to disease progression, and 2 for other reasons.


  1. Palumbo, Antonio, MD, et al. “175 Weekly Carfilzomib, Cyclophosphamide and Dexamethasone (wCCd) in Newly Diagnosed Multiple Myeloma Patients: A Phase I- II Study.” ASH 2014. Oral Presentation. December 7, 2014.