Final results from a Phase 2 study show that Kyprolis can be an effective treat­ment for re­lapsed and refractory multiple myeloma patients, with nearly a quarter of these patients responding to treat­ment.

Dr. David Siegel, from the John Theurer Cancer Center and lead investigator of the study, said the results dem­onstrate that Kyprolis ^[1] (car­filz­o­mib) has “excellent activity with low toxicity.”

Based on the results of this study, the U.S. Food and Drug Administration recently approved Kyprolis for use in re­lapsed and refractory multiple myeloma patients (see related Beacon ^[2] news).

“Patients can be happy that there is another treat­ment option available to them,” said Dr. Sergio Giralt from the Memorial-Sloan Kettering Cancer Center.  In particular, Dr. Giralt, who was not involved with the study, noted, “For patients with neu­rop­athy, there is an alter­na­tive agent to bor­tez­o­mib [Velcade] that does not cause neu­rop­athy [pain, tingling, or loss of sensation in the extremities].”

In addi­tion, Dr. Giralt was optimistic about the durability of the responses to Kyprolis.

Kyprolis, which is being marketed by Onyx Pharmaceuticals (NASDAQ: ONXX), works similarly to Velcade ^[3] (bor­tez­o­mib).  Both are proteasome inhibitors that prevent the breakdown of proteins in cancer cells, triggering their death.

From July 2008 until October 2009, 266 re­lapsed and refractory myeloma patients who had received a median of five prior ther­a­pies were enrolled in the study. All patients had pre­vi­ously received Velcade as well as Revlimid ^[4] (lena­lido­mide) or thalidomide ^[5] (Thalomid), and all patients were refractory (resistant) to their most recent ther­apy.

Study participants received 20 mg/m² of Kyprolis twice a week for three weeks followed by a week off during the first treat­ment cycle.  Doses were then increased to 27 mg/m² during sub­se­quent treat­ment cycles, for up to a total of 12 cycles.

Participants also received 4 mg of dexamethasone ^[6] (Decadron) prior to each Kyprolis dose during the first treat­ment cycle, and as needed afterwards, to prevent potential infusion reactions. The pre-infusion dexa­meth­a­sone doses were not permitted, however, to exceed 4 mg.

Overall, 23 per­cent of the patients responded to Kyprolis, with 0.4 per­cent achieving a complete response, 5 per­cent a very good partial response, and 18 per­cent a partial response. Moreover, 15 per­cent of patients who were refractory to both Velcade and Revlimid responded.  The median duration of response for both groups was 7.8 months.

Dr. Siegel explained that the low complete response rate is not surprising, given how heavily pretreated these patients were. “The fact that patients tolerate long-term use will translate into higher complete response rates.  More significantly, it will translate into better long-term disease control, which is the ultimate goal in patients with refractory/relapsed disease,” he added.

The median pro­gres­sion-free survival time was 3.7 months.

The median over­all survival time was 15.6 months across all patients included in the study, and 11.9 months for patients refractory to both Velcade and Revlimid.  The investigators noted that the median over­all survival time observed in their study compares favorably to the 9 months typically observed in this type of patient population.

The most common side effects of Kyprolis treat­ment were fatigue (49 per­cent), low red blood cell counts (46 per­cent), nausea (45 per­cent), and low platelet counts (39 per­cent).

Prior to the study, 77 per­cent of the participants had periph­eral neu­rop­athy, but only 12 per­cent of patients experienced new-onset or worsening of existing neu­rop­athy during treat­ment with Kyprolis.

In addi­tion, 2 per­cent of the patients died due to cardiac arrest, breathing difficulty, or liver failure that may be linked to Kyprolis admin­istra­tion.

Dr. Giralt believes Kyprolis’s safety profile should not be a concern. “We all have to remember that these treat­ments come with many side effects. However, [the study investigators] dem­onstrated safe admin­istra­tion of the correct dose, as seen by the safety profile,” he said.

After completing the planned 12 cycles of Kyprolis treat­ment, 12 per­cent of the study participants went on to be treated with Kyprolis in an extension study.

Results from the Phase 2 trial in com­bi­na­tion with pre­vi­ous trials indicate that higher doses of Kyprolis are more effective, so ongoing and future studies are testing higher doses of the drug.

Kyprolis is also being studied in com­bi­na­tion with Revlimid and dexa­meth­a­sone for re­lapsed and refractory myeloma patients as well as newly diagnosed patients.

For more in­­for­ma­tion, please refer to the study in the journal Blood ^[7] (pdf). For more in­­for­ma­tion on all ongoing Kyprolis trials in multiple myeloma, please see the U.S. Clinical Trials Registry ^[8].