Researchers affiliated with the Multiple Myeloma Research Consortium (MMRC) have reported that carfilzomab monotherapy is highly active in patients with relapsed myeloma and can be administered safely for at least one year in responding patients. The details of this study were presented at the Joint ECCO 15-34^th ESMO Multidisciplinary Congress in Berlin, September 20-24, 2009.[1]

The currently available proteasome inhibitor, Velcade® (bortezomib), has excellent clinical activity in patients with multiple myeloma and mantle cell lymphoma and is currently being evaluated in combination with other agents in patients with solid tumors. Carfilzomib is a new proteasome inhibitor that is currently undergoing Phase I-II testing in patients with myeloma and solid tumors.

At the 2008 meeting of the American Society of Hematology (ASH) and the 2009 meeting of the American Society of Clinical Oncology (ASCO), researchers affiliated with the MMRC reported that carfilzombib was effective for patients with relapsed or refractory myeloma.[2] This study included 46 patients who had failed Velcade as well as Thalomid® (thalidomide) or Revlimid® (linalidomide). Eighty-three percent of patients in this study had also failed a stem cell transplant. The clinical benefit rate was 26%, with five patients achieving a partial response. Time to tumor progression was 6.2 months.

Another study presented at ASH 2008 and ASCO 2009 involved 31 patients who were characterized as Velcade naïve, Velcade responsive, or Velcade resistant.[3] The overall response rate for 14 Velcade naïve patients was 57%, with one complete response, two very good partial response, and five partial responses. Median time for tumor progression had not been reached. For 17 patients who had previously received Velcade, the overall response rate was 18%. Three had a partial response, one had a minimal response, and nine had stable disease. Time to tumor progression was 8.9 months.

At the ECCO-15 -34^th ESMO Congress, the preliminary results of an ongoing Phase I dose-escalation trial combining carfilzomib with Revlimid and low-dose dexamethasone in patients with relapsed myeloma were presented.[4] This study utilized a fixed dose of carfilzomib and dexamethasone with escalating Revlimid. Eighteen patients were treated at three dose levels, and six of these patients had a partial response.

The current study presented at ECCO-ESMO 2009 was a follow-up of the 31 patients presented at ASH 2008 and AASCO 2009. Carfilzomib was administered on days 1, 2, 8, 9, 15, and 16 in a 28-day cycle for up to 12 cycles. Fourteen patients had not received Velcade, and 17 had received Velcade. Fifteen of the 17 patients who had received Velcade had failed an autologous stem cell transplant. At the time of the abstract, the average number of treatment cycles was 6.6, with 11 patients reaching 12 cycles. The most common side effects were fatigue, nausea, and vomiting. The main new observation of this presentation was that the 30% patients who responded to carfilzomib tolerated full-dose therapy without disease progression for at least one year, which was the end of the study.

Comments: These data suggest that carfilzomib may become the second protease inhibitor to prove useful for multiple myeloma. There will probably be future head-to-head comparisons to determine if there are any advantages to carfilzomib over Velcade.

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