Preliminary results from an ongoing Phase 1b clinical trial suggest that carfilzomib (Kyprolis) in com­bi­na­tion with Revlimid (lena­lido­mide) and low-dose dexamethasone (Decadron) is well-tolerated over extended periods of ther­apy in patients who have re­lapsed or are resistant (refractory) to pre­vi­ous myeloma treat­ment.

The findings were presented Friday at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

Carfilzomib is a new ther­apy being developed by Onyx Pharmaceuticals and studied for the treat­ment of patients with re­lapsed or refractory myeloma. It works similarly to Velcade (bor­tez­o­mib) by preventing the breakdown of protein in cancer cells, triggering their death. In clinical trials cur­rently underway with the drug, treat­ment with car­filz­o­mib results in less damage to the periph­eral nervous system and fewer cases of low white blood cells than other cur­rently approved multiple myeloma ther­a­pies.

The goal of this Phase 1b study was to determine the safety and maximum recommended dose of car­filz­o­mib admin­istered with Revlimid and low-dose dexa­meth­a­sone, a regi­men abbreviated CRd, in patients with re­lapsed or refractory myeloma. The researchers also studied the efficacy of CRd in these patients.

Results published in the ASCO abstract report on safety and efficacy results for 40 patients. The results presented today at the meeting include an addi­tional 44 patients enrolled in the expansion phase of the trial, further testing full-dose CRd.

All patients enrolled in this clinical trial were pre­vi­ously treated, most with Velcade, Revlimid, or thalidomide (Thalomid). Among the initial 40 participants, 47 per­cent were refractory to their last ther­apy, and 84 per­cent had a history of nerve damage to the limbs related to pre­vi­ous treat­ments. Patients were given different doses of the CRd com­bi­na­tion ther­apy in a 28-day cycle.

Researchers found that at the full dose of CRd, 6 per­cent of patients showed a complete response, 27 per­cent showed a very good partial response, and 42 per­cent showed a partial response for an over­all response rate of 75 per­cent. They also found that this response improved with long-term ther­apy (up to 18 cycles of treat­ment).

More than a third of the patients have received CRd for more than a year and are still participating in the study. All of these patients, however, received reduced doses of car­filz­o­mib and Revlimid.

Researchers did not observe any dose-limiting side effects over an extended period of treat­ment (14 to 23 months). None of the patients showed signs of severe nerve damage, blood clotting, or fatigue. Although some patients experienced seriously low levels of white blood cells (23 per­cent of patients), platelets (18 per­cent), and red blood cells (12 per­cent), researchers found that levels returned to normal after treat­ment.

Based on the results of this Phase 1b study, researchers concluded that full-dose CRd was well-tolerated in re­lapsed/refractory myeloma patients, including patients heavily pretreated with Velcade, Revlimid, or thalido­mide as well as patients with a history of treat­ment-related nerve damage. Additionally, CRd was well-tolerated throughout long-term treat­ment.

The researchers added that CRd is effective in patients pre­vi­ously treated with Velcade, Revlimid, or thalido­mide.

A phase 3 trial comparing full-dose CRd with Rd will begin recruiting patients later this year.

For more in­­for­ma­tion, please see abstract 829 on the ASCO meeting website.