Carfilzomib, which is a proteasome inhibitor under devel­op­ment as a treat­ment for multiple myeloma, has recently been shown to be a safe and effective treat­ment for myeloma patients with kidney failure, chromosomal ab­nor­mal­i­ties, or periph­eral neu­rop­athy. These results will be presented at the 51st American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans December 5 through 8.

Additionally, ASH presenters will examine the effects of car­filz­o­mib in patients who have pre­vi­ously been treated with Velcade (bor­tez­o­mib) and in patients who are receiving car­filz­o­mib in com­bi­na­tion with Revlimid (lena­lido­mide) and dexamethasone (Decadron). These results were discussed in Part 1 of this article.

Carfilzomib Is Safe And Effective For Myeloma Patients With Kidney Failure

More than 20 per­cent of newly diagnosed myeloma patients suffer from kidney failure, and more than 50 per­cent of myeloma patients experience kidney failure at some point during the course of their disease. Therefore, it is important for myeloma treat­ments to be tested in patients with kidney problems.

A Phase 1 study examined the effects of car­filz­o­mib on re­lapsed myeloma patients with kidney impairment. Patients were placed into four groups, those with normal kidney function, or mild, mod­er­ate, or severe kidney impairment. Patients requiring dialysis were included in the severe group.

Eighteen patients were evaluated for response to the treat­ment, and the over­all response rate was 17 per­cent.

The most common side effects were fatigue, low red blood cell counts, back pain, and fever. Side effects did not vary depending on the severity of kidney impairment. No patients experienced new or worse periph­eral neu­rop­athy.

Two patients dis­con­tinued ther­apy due to increased kidney failure related to disease pro­gres­sion, and there were three deaths, including two caused by disease pro­gres­sion and one from an in­fec­tion.

The study concluded that car­filz­o­mib is safe in patients with kidney problems and the same dose can be used for patients with or without kidney impairment.

For more in­­for­ma­tion, see ASH abstract 3877.

Chromosomal Abnormalities Do Not Affect Carfilzomib Efficacy

Chromosomal ab­nor­mal­i­ties can affect whether a myeloma patient responds to treat­ment. This study assessed the effects of car­filz­o­mib on re­lapsed and refractory multiple myeloma patients with and without cytogenetic (chromosomal) ab­nor­mal­i­ties.

There were 79 patients enrolled in the study. Of the total number of participants, 23 had one or more chromosomal ab­nor­mal­i­ties asso­ci­ated with multiple myeloma.

Results from the study showed that chromosomal ab­nor­mal­i­ties do not negatively affect the efficacy of car­filz­o­mib. The response rates of those with chromosomal ab­nor­mal­i­ties and those without – 44 per­cent and 39 per­cent, respectively – were not significantly different. Likewise, time to disease pro­gres­sion was similar for both groups – 195 days for those with chromosomal ab­nor­mal­i­ties and 208 days for those without.

For more in­­for­ma­tion, see ASH abstract 1827.

Carfilzomib Causes Minimal Peripheral Neuropathy

Peripheral neu­rop­athy can be a serious side effect of several myeloma treat­ments. Peripheral neu­rop­athy is nerve damage that can cause tingling, pain, loss of muscle control, and loss of feeling in the hands and feet.

Carfilzomib was studied to determine if the drug causes periph­eral neu­rop­athy or worsens a preexisting con­di­tion of nerve damage.

At the start of the study, 54 per­cent of patients had mild or mod­er­ate periph­eral neu­rop­athy caused by pre­vi­ous treat­ment.

After treat­ment with car­filz­o­mib, 15 per­cent of patients reported periph­eral neu­rop­athy, with 9 per­cent possibly asso­ci­ated with car­filz­o­mib treat­ment. Severe neu­rop­athy was reported in 2 per­cent of patients. No patients required a dose reduction or dis­con­tinued treat­ment due to periph­eral neu­rop­athy.

For more in­­for­ma­tion, see abstract 430 on the ASH meeting Web site and Part 1 of this series.