The results of a Phase 1 study show that Kepivance reduces the severity of melphalan-related mouth ulcers in multiple myeloma patients. Due to better tolerability, the melphalan dosage could be safely increased to 280 mg/m² prior to a stem cell transplant.

Almost two-thirds of the patients, who all had normal kidney function, had responded to the regimen at 100 days post transplant. The study investigators point out, however, that a Phase 2 trial will be necessary to better determine the efficacy of this regimen.

High-dose chemotherapy followed by autologous stem cell transplantation is the standard course of treatment for multiple myeloma patients under the age of 65. Patients with normal kidney function typically receive a preparative regimen of 200 mg/m² of melphalan ^[1] (Alkeran) before a transplant.

Previous attempts to increase the melphalan dose to improve treatment outcomes have been limited by the development of dose-limiting side effects, such as severe mouth ulcers and disrupted heart rhythms. Severe mouth ulcers can cause patients to require hospitalization in order to receive nutrition intravenously.

Kepivance ^[2] (palifermin) is a drug that stimulates the growth of cells lining the mouth and intestinal tract. In a previous study, it was found to reduce mouth ulcers in myeloma patients receiving a standard dose of melphalan (see related Beacon ^[3] news).

Researchers led by Dr. Muneer Abidi at the Karmanos Cancer Institute in Detroit, Michigan, designed a study to identify the maximum tolerated dose of melphalan in multiple myeloma patients who also received Kepivance. The researchers hypothesized that a higher dose of melphalan could be tolerated if taken in combination with Kepivance, which could potentially lead to improved disease outcomes.

While Kepivance is costly, the study authors believe the cost could be justified if its use improves response to treatment, decreases time in the hospital, and reduces the need for supportive care for patients with severe mouth ulcers.

Nineteen patients with a median age of 49 years were enrolled in this study between May 2007 and September 2009. They each received 60 µg/kg of Kepivance for three days before the transplant and for three days after the transplant. Patients received between 200 mg/m² and 280 mg/m² of melphalan two days before the transplant.

Overall, 18 patients completed the study and were assessed 100 days after the transplant.

At 100 days post transplant, 61 percent of patients had responded to the treatment, including 17 percent who achieved a complete response, 17 percent a very good partial response, and 27 percent a partial response.

Overall, 44 percent of the patients developed severe mouth ulcers for a median duration of five days. Out of the six patients who received the highest dose of melphalan, only 17 percent developed severe mouth ulcers. Twenty-eight percent of the patients did not experience any mouth ulcers.

According to the investigators, the overall rate of severe mouth ulcers is comparable to that of a previous study, which showed that severe mouth ulcers occurred in 42 percent of newly diagnosed myeloma patients receiving 200 mg/m² of melphalan.

Since the median duration of the severe ulcers in the current study was only five days, no patients required intravenously administered nutrition.

The most common Kepivance-related side effects included mild to moderate rash (100 percent), elevation of enzymes including amylase (56 percent) and lipase (28 percent), and mild to moderate swelling (61 percent).

Irregular heartbeat, which may have been a melphalan-related complication, occurred in 17 percent of patients treated with 280 mg/m2 of melphalan.

The researchers did not observe any treatment-related deaths.

For more information, please see the study in Biology of Blood and Marrow Transplantation ^[4] (abstract).