Results of a Phase 1 clinical trial suggest that the investigational drug LY2127399 in combination with Velcade is safe and effective enough to deserve further study as a potential treatment for multiple myeloma.

“We are very encouraged by these results and would like to move this forward to a randomized trial comparing LY2127399 and Velcade with Velcade alone,” said Dr. Noopur Raje, from Dana-Farber Cancer Institute when she presented these findings at the 47^th Annual Meeting of the American Society of Clinical Oncology (ASCO) on Sunday.

Dr. Nikhil Munshi from the Dana-Farber Cancer Institute said in a summary talk about potential new myeloma treatments that he was also encouraged by these first results. However, he pointed out that larger studies are needed to confirm the results and to determine if LY2127399 and Velcade act synergistically to overcome resistance in Velcade-refractory patients.

LY2127399, a new drug that is being developed by the U.S. pharmaceutical company Eli Lilly, neutralizes the effects of the B-cell activating factor (BAFF) protein found on the surface of immune cells. BAFF, which stimulates myeloma cell growth and resistance to chemotherapy, tends to be present at higher levels in the blood of approximately 60 percent of myeloma patients.

The study authors aimed to determine the optimal dose of LY2127399 in combination with Velcade ^[1] (bortezomib) for previously treated myeloma patients.

The study enrolled 20 patients with a median age of 66 years who had received a median of three prior therapies. Sixty-five percent of patients received prior treatment with Velcade, and 90 percent had received either Revlimid ^[2] (lenalidomide) or thalidomide ^[3] (Thalomid) before.

All patients received either 1 mg, 10 mg, 30 mg, 100 mg, or 300 mg of LY2127399 intravenously on day 1 for the first three treatment cycles and then every other cycle going forward.  In addition, all patients received 1.3 mg/m² Velcade intravenously on days 1, 4, 8, and 11 of each 21-day treatment cycle. Patients have received a median of five treatment cycles so far.

The overall response rate after treatment was 55 percent; 10 percent of participants achieved a complete response, 15 percent achieved a very good partial response, and 30 percent achieved a partial response.

“Even though this was a Phase 1 study, we were very encouraged to see pretty significant responses,” said Dr. Raje.

Median time to disease progression was 4.9 months. Dr. Raje pointed out that a few patients progressed early after starting treatment. “If patients responded to treatment, they were able to continue on this treatment for a fairly long time,” she added.

The study authors determined that the optimal dose for LY2127399 in combination with Velcade was 100 mg.

According to Dr. Raje, LY2127399 was well tolerated. “We had no infusion-related reactions with LY2127399,” she said. “Most of the side effects were very well managed.”

The most common severe side effects included low platelet counts (20 percent), low white blood cell counts (15 percent), pain and tingling sensations in the extremities (15 percent), and diarrhea (10 percent).

“The safety profile of LY2127399 in combination with Velcade was very similar to what you see with Velcade as a single agent,” she explained.

One of the patients who experienced low platelet counts and all patients who had pain and tingling in the extremities discontinued treatment. One patient discontinued treatment because of progressive disease.

For more information, see abstract 8012 ^[4] on the ASCO meeting ^[5]website.