Preliminary results from several clinical trials testing carfilzomib ^[1] (Kyprolis ^[2]) for the treat­ment of multiple myeloma will be presented at the 51st American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans December 5 through 8.

Carfilzomib, a proteasome inhibitor, is under devel­op­ment as a treat­ment for re­lapsed or refractory multiple myeloma. It is cur­rently in Phase 2 of clinical testing, which means that its safety and efficacy are being studied.

The ASH presenters will examine the effects of car­filz­o­mib in patients who have pre­vi­ously been treated with Velcade ^[3] (bor­tez­o­mib); in patients who are receiving car­filz­o­mib in com­bi­na­tion with Revlimid ^[4] (lena­lido­mide) and dexamethasone ^[5] (Decadron); and in patients with kidney failure, chromosomal ab­nor­mal­i­ties, or periph­eral neu­rop­athy. Carfilzomib for the treat­ment of patients with specific con­di­tions will be presented in Part 2 ^[6] of this series.

Carfilzomib As A Single Agent

One of the studies that will be presented at the ASH meeting is a Phase 2 study examining the effectiveness of car­filz­o­mib in the treat­ment of re­lapsed or refractory myeloma patients. The participants were split into two groups: those who had pre­vi­ously been treated with Velcade and those who had not.

Participants received 20 mg/m² of intravenous car­filz­o­mib on days 1, 2, 8, 9, 15, and 16 of a 28 day cycle for up to 12 cycles.

Prior Treatment With Velcade

Thirty-three participants who had pre­vi­ously been treated with Velcade were evaluated for their response to car­filz­o­mib treat­ment. It was determined that 18 per­cent experienced a complete or partial response, meaning they experienced either remission or a significant decrease in clinical indicators of cancer.

The side effects observed most frequently in this study were fatigue (57 per­cent of participants) and nausea (54 per­cent). More severe side effects such as low red blood cell counts (14 per­cent), low white blood cell counts (11 per­cent), and periph­eral neu­rop­athy (11 per­cent) were observed. Peripheral neu­rop­athy is nerve damage that can result in numbness and pain in the hands and feet. Among patients with kidney failure, none had to dis­con­tinue car­filz­o­mib treat­ment.

The results of this group indicate that car­filz­o­mib could potentially be a safe and effective treat­ment for patients who do not respond to Velcade.

No Prior Treatment With Velcade

The second group of 57 study participants all had re­lapsed or refractory multiple myeloma but had not been pre­vi­ously treated with Velcade. Of the 51 patients evaluated, 45 per­cent experienced complete response, very good partial response, or partial response.

Like the Velcade group, the most common side effects were fatigue (59 per­cent) and nausea (41 per­cent), and a similar per­cent­age of patients experienced periph­eral neu­rop­athy (12 per­cent). The 12 patients who had poor kidney function coming into the study tolerated car­filz­o­mib well.

The study authors highlighted that a response rate of 45 per­cent is noteworthy for a single-agent treat­ment for patients who have not have success with other ther­a­pies.

This study is still underway and is cur­rently recruiting new participants. Based on the dem­onstrated safety of car­filz­o­mib, participants may now receive 27 mg/m², an increase from the original dose of 20 mg/m².

For more in­­for­ma­tion, see the ASH abstracts 303 ^[7] (Velcade refractory) and 302 ^[8] (Velcade-naïve). To enroll in this study, see the United States Clinical Trials ^[9] Web site.

Carfilzomib In Combination With Revlimid And Dexamethasone

A Phase 1B study was conducted to assess the safety of car­filz­o­mib in com­bi­na­tion with Revlimid and low dose dexa­meth­a­sone in re­lapsed or refractory myeloma patients.

The participants, split into groups, received a com­bi­na­tion regi­men of 15 to 27 mg/m² intravenous car­filz­o­mib, 10 to 25 mg Revlimid, and 40 mg low dose dexa­meth­a­sone. The six different dose com­bi­na­tions of car­filz­o­mib and Revlimid will help determine the maximum dosages that should be admin­istered to maintain effectiveness as well as a low rate of serious side effects.

It was determined that re­lapsed myeloma patients can tolerate a com­bi­na­tion of 20 mg/m² car­filz­o­mib, 25 mg Revlimid, and low dose dexa­meth­a­sone. Several participants are cur­rently receiving 27 mg car­filz­o­mib, 25 mg Revlimid, and low dose dexa­meth­a­sone to determine the safety of that com­bi­na­tion. Because car­filz­o­mib and Revlimid do not have overlapping toxicities, full doses of these regi­mens over long periods of time (greater than 10 months) are possible.

Based on the results of this trial, a Phase 3 trial is being planned for early 2010 that will test car­filz­o­mib, Revlimid, and dexa­meth­a­sone compared to Revlimid and dexa­meth­a­sone without car­filz­o­mib.

For more in­­for­ma­tion, see abstract 304 ^[10] on the ASH meeting Web site and Part 2 ^[6] of this series.