An ongoing Phase 2 trial of carfilzomib ^[1] has dem­onstrated that car­filz­o­mib may be effective in treating re­lapsed/refractory multiple myeloma patients, including patients who are resistant to or re­lapsed after Velcade ^[2] (bor­tez­o­mib) treat­ment. The results were presented by Dr. Ravi Vij of Washington University in St. Louis at the annual American Society of Clinical Oncology (ASCO) meeting in Chicago on June 5.

“Single agent car­filz­o­mib has dem­onstrated significant activity in re­lapsed/refractory myeloma,” said Dr. Vij during his presentation.

Carfilzomib, developed by Onyx Pharmaceuticals ^[3], is a new drug cur­rently being in­ves­ti­gated as a potential multiple myeloma ther­apy. Similar to Velcade, it is a proteasome inhibitor that prevents the growth and spread of myeloma cells by interrupting their protein-related cellular processes. However, car­filz­o­mib triggers this response by binding to different proteins than those bound by Velcade.

Because car­filz­o­mib yields the same thera­peutic response as Velcade via an alter­na­tive mechanism, this Phase 2 trial in­ves­ti­gated its potential for success in multiple myeloma patients for whom Velcade treat­ment has failed.

In the study, the effects of car­filz­o­mib treat­ment were in­ves­ti­gated in three separate patient groups. The first group consisted of 35 participants who had already undergone Velcade treat­ment, 14 of whom were resistant to the most recent treat­ment. The second and third groups, who received different doses of car­filz­o­mib, consisted of 54 and 20 patients, respectively, who had never received Velcade treat­ment.

Participants in all three groups received 20 mg/m² of car­filz­o­mib by infusion twice a week for three weeks followed by a week of rest during the first cycle. Patients in the third group received 27 mg/m² of car­filz­o­mib in sub­se­quent cycles. In all groups, this 28-day cycle was repeated five times.

The two groups that had no prior exposure to Velcade had over­all response rates of 45 per­cent (low dose) and 55 per­cent (high dose). The over­all response rate for the first group, which had been treated with Velcade prior to the trial, was 21 per­cent.

While the over­all response rate to car­filz­o­mib in patients who had been pre­vi­ously treated with Velcade was lower than the over­all response rate of the other two groups, researchers still believe these results may be significant.

At the lower dose of car­filz­o­mib, duration of response was similar between patients with prior Velcade ther­apy and patients without prior Velcade ther­apy who achieved at least a minimal response: 8.5 months versus 8.3 months. Increasing the dose of car­filz­o­mib extended duration of response to 11.5 months.

In his presentation, Dr. Vij explained that although the response elicited by the first group was minimal, car­filz­o­mib may still be a reasonable treat­ment for re­lapsed and refractory multiple myeloma patients. “We know that patients with minimal responses have a survival advantage over patients that have no response. Minimal response that is durable is perhaps of clinical utility.”

Most side effects were mild and man­ageable. The most common severe side effects were low red blood cell count (10 per­cent of patients), low platelet count (10 per­cent), and low white blood cell count (10 per­cent). Mild to mod­er­ate side effects included fatigue (66 per­cent of participants), nausea (49 per­cent), shortness of breath (40 per­cent), low red blood cell count (34 per­cent), and diarrhea (32 per­cent). Fever and treat­ment-related periph­eral neu­rop­athy (pain and tingling in the extremities) were uncommon.

Due to a lack of significant side effects, Dr. Vij concluded that side effects would still be man­ageable with the addi­tion of other drugs to the regi­men. “This tolerability suggests that [carfilzomib] can be used favorably in com­bi­na­tion ther­a­pies,” said Dr. Vij.

Also due to the good tolerability, car­filz­o­mib will likely be studied at higher doses in upcoming trials. Dr. Vij expects higher response rates with higher doses.

For more in­­for­ma­tion, please see abstract 8000 ^[4] on the ASCO meeting ^[5] website.