Results of a Phase 2 clin­i­cal trial show that elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone is safe and ef­fec­tive in re­lapsed / refractory mul­ti­ple myeloma patients.

“Elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone has a very high re­sponse rate,” said Dr. Philippe Moreau from the Uni­ver­sity Hospital in Nantes, France, when he pre­sented the findings at the 47^th Annual Meeting of the American Society of Clinical Oncology (ASCO) on Sunday.

“[The com­bi­na­tion] seems to be superior to Revlimid plus high-dose dexa­meth­a­sone,” he added.

In a summary talk about po­ten­tial new myeloma treat­ments, Dr. Nikhil Munshi from the Dana-Farber Cancer In­sti­tute was enthusiastic about the study re­­sults. “Elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone appears to be very promising,” he said.

He pointed out that it would be in­ter­est­ing to see if this drug also has single-agent ac­­tiv­ity.

Elotuzumab ^[1] is a drug under de­vel­op­ment by Bristol-Myers Squibb that identifies pro­teins on the surface of myeloma cells and incites the im­mune sys­tem to destroy the cancer cells.

Results of the preceding Phase 1 study showed that 82 per­cent of re­lapsed / refractory myeloma patients responded to elotuzumab in com­bi­na­tion with Revlimid ^[2] (lena­lido­mide) and dexamethasone ^[3] (Decadron).

Interim re­­sults of both the Phase 1 and Phase 2 trials were pre­sented at the American Society of He­ma­tol­ogy annual meeting last De­cem­ber (see re­lated Beacon ^[4] news).

The ran­dom­ized Phase 2 study en­rolled 98 re­lapsed / refractory myeloma patients with a median age of 62 years. Patients had re­ceived a median of two prior ther­a­pies. Two-thirds of patients had prior Velcade ^[5] (bor­tez­o­mib) ther­apy, and 60 per­cent had prior thalidomide ^[6] (Thalomid) ther­apy, while patients who were pre­vi­ously treated with Revlimid were excluded from the study.

Half of the patients re­ceived 10 mg/kg in­tra­venous elotuzumab, and the other half re­ceived 20 mg/kg. Patients re­ceived elotuzumab on days 1, 8, 15, and 22 of the first two 28-day cycles and on days 1 and 15 of sub­se­quent cycles.

In addi­tion, they re­ceived 25 mg oral Revlimid on days 1 to 21, along with 40 mg low-dose dexa­meth­a­sone once per week.

The patients were also given anti-in­flam­ma­tory drugs prior to elotuzumab in order to prevent the elotuzumab-related in­fusion reac­tions observed in the Phase 1 trial.

Patients con­tinued to re­ceive treat­ment until their dis­ease progressed or until they ex­peri­enced severe side effects.

The study authors found that 82 per­cent of patients responded to treat­ment, with 9 per­cent of patients achieving a com­plete re­sponse, 33 per­cent a very good partial re­sponse, and 40 per­cent a partial re­sponse.

However, the re­sponse rate was higher for the 10 mg/kg group than the 20 mg/kg group (92 per­cent versus 75 per­cent. Based on these findings, Dr. Moreau and his colleagues rec­om­mended the 10 mg dose for the Phase 3 trial.

Additionally, among patients who had re­ceived one prior ther­apy, the over­all re­sponse rate was 90 per­cent. “This [finding] provides the rationale for investigating this com­bi­na­tion earlier in the course of the dis­ease, as part of a front-line treat­ment,” he ex­plained.

The median time to re­sponse was 30 days, which Dr. Moreau described as short.  

With a median follow-up of nine months, the median pro­gres­sion-free sur­vival has not been reached yet.

According to Dr. Moreau, the treat­ment was well tol­er­ated. The most common severe side effects in­cluded low white blood cell counts (20 per­cent), low platelet counts (17 per­cent), and low red blood cell counts (10 per­cent).

“The main side effects are re­lated to the Revlimid use,” ex­plained Dr. Moreau.

Elotuzumab-related side effects in­cluded nausea (16 per­cent), dizzi­ness (13 per­cent), and fever (10 per­cent).

Thirty-nine per­cent of patients stopped treat­ment, mainly due to dis­ease pro­gres­sion or side effects.

For more in­for­ma­tion, see abstract 8014 ^[7] on the ASCO meeting ^[8]website.