The re­­sults of three on­go­ing clin­i­cal trials sug­gest that elotuzumab in com­bi­na­tion with either Velcade (bor­tez­o­mib) or Revlimid (lena­lido­mide) plus low-dose dexamethasone (Decadron) is ef­fec­tive and well-tolerated in patients who have re­lapsed or have treat­ment-resistant mul­ti­ple myeloma.

The findings were pre­sented at the American Society of He­ma­tol­ogy (ASH) annual meeting in Orlando last week.

Elotuzumab is a new drug being devel­oped by Facet Biotech and Bristol-Myers Squibb as a po­ten­tial treat­ment for mul­ti­ple myeloma. It recog­nizes and binds to unique pro­teins on the surface of mul­ti­ple myeloma cells. The im­mune sys­tem can then target and destroy the can­cer­ous cells.

Elotuzumab In Com­bi­na­tion With Velcade

Dr. Andrzej Jakubowiak, from the Uni­ver­sity of Michigan, pre­sented a poster with up­dated re­­sults from a Phase 1 clin­i­cal trial studying elotuzumab in com­bi­na­tion with Velcade in re­lapsed and re­frac­tory myeloma patients.

A total of 28 myeloma patients with an average of two prior ther­a­pies were en­rolled in the study.  Of the 28 patients, 11 had re­ceived prior Velcade treat­ment and four of the 11 were resistant to Velcade.

The patients re­ceived es­ca­lat­ing doses of elotuzumab (from 2.5 mg/kg to 20 mg/kg) on days 1 and 11 and a fixed-dose of Velcade (1.3 mg/m²) on days 1, 4, 8, and 11 of a 21-day cycle. Dexa­meth­a­sone was added for patients who ex­peri­enced dis­ease pro­gres­sion early in the trial. 

Forty-eight per­cent of patients achieved a partial re­sponse or better, 7 per­cent of whom achieved a com­plete re­sponse.  Notably, a partial re­sponse was also observed in 50 per­cent of Velcade-resistant patients.

The median time to dis­ease pro­gres­sion was 9.5 months, both for the over­all study group and the Velcade-resistant group.

All admin­istered doses of elotuzumab were well tol­er­ated.  The most common severe treat­ment-related side effects were fatigue, diarrhea, nausea, pneu­monia, low platelet counts, con­sti­pa­tion, low red blood cell counts, periph­eral neu­rop­athy (pain and tingling in the legs, arms, hands, and feet), and low white blood cell counts.

Preliminary study re­­sults were pre­sented at the American Society of Clinical Oncology meeting this summer (see re­lated Beacon news).

Elotuzumab In Com­bi­na­tion With Revlimid And Low-Dose Dexa­meth­a­sone – Phase 1 Trial

Dr. Sagar Lonial, from the Emory Winship Cancer In­sti­tute, pre­sented a poster with up­dated re­­sults from an on­go­ing Phase 1 clin­i­cal trial studying elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone in re­lapsed and re­frac­tory myeloma patients.

The study in­cluded 29 ad­vanced myeloma patients who had undergone an average of three prior treat­ments.  They re­ceived 5, 10, or 20 mg/kg elotuzumab weekly for the first two treat­ment cycles and then every other week for sub­se­quent cycles. Patients also re­ceived Revlimid (25 mg) on days 1 to 21 of a 28-day cycle and low-dose dexa­meth­a­sone (40 mg) once a week.

Patients re­ceived a median of 8.5 treat­ment cycles. 

Dr. Lonial and his colleagues found that 82 per­cent of patients achieved a partial re­sponse or better. Of the patients who had not re­ceived prior Revlimid treat­ment, 96 per­cent achieved a partial re­sponse or better. Over­all re­sponse rates were also high in patients who had re­ceived prior thalidomide (Thalomid) treat­ment or were re­frac­tory to their most recent ther­apy, 94 per­cent and 82 per­cent, re­spec­tively. 

Among all the treat­ment groups, 53 per­cent of patients had not progressed at 16 months.  Of the patients who re­ceived the highest dose of elotuzumab (20 mg), 66 per­cent had not progressed at 16 months.  The median time to dis­ease pro­gres­sion has not yet been reached.

The most common severe side effects were low white blood cell and platelet levels, ex­peri­enced by 36 per­cent and 21 per­cent of study par­tic­i­pants, re­spec­tively. In addi­tion, two patients ex­peri­enced serious in­fusion-related reac­tions.

Preliminary study re­­sults were pre­sented at the American Society of Clinical Oncology meeting this summer (see re­lated Beacon news).

Elotuzumab In Com­bi­na­tion With Revlimid And Low-Dose Dexa­meth­a­sone – Phase 2 Trial

Dr. Paul Richardson, from the Dana-Farber Cancer In­sti­tute, pre­sented interim re­­sults of the Phase 2 study of elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone in re­lapsed / refractory patients.

“What was par­tic­u­larly im­por­tant [about this Phase 2 trial] is that the high over­all re­sponse rates that had been seen in Phase 1 were reproduced in this larger, multi­center trial, with a remarkable over­all re­sponse rate and very high quality re­sponse rate,” said Dr. Richardson.

A total of 63 re­lapsed / refractory mul­ti­ple myeloma patients have been en­rolled in the study.  Patients pre­vi­ously treated with Revlimid were excluded from the trial.

Half of the study par­tic­i­pants re­ceived 10 mg/kg elotuzumab, and the other half re­ceived 20 mg/kg.  Patients re­ceived treat­ment once a week for the first two 28-day cycles and once every other week for all sub­se­quent cycles.

Patients were premedicated with anti-in­flam­ma­tory drugs prior to elotuzumab in­fusion in an attempt to con­trol in­fusion-related side effects, which had been observed in the Phase 1 trial. 

Ninety per­cent of patients re­ceiv­ing the 10 mg/kg dose achieved at least a partial re­sponse, com­pared to 72 per­cent for those re­ceiv­ing the 20 mg/kg dose.  According to Dr. Richardson, time to re­sponse was very rapid, at a median of two months.

The median pro­gres­sion-free sur­vival was not reached during the 4.9 months of follow-up, which ac­cord­ing to Dr. Richardson is very en­cour­ag­ing for this patient pop­u­la­tion. He added that it was more than one year in the Phase 1 trial.

Side effects were man­ageable in the majority of patients and were predominantly side effects seen with Revlimid and dexa­meth­a­sone. 

The most common elotuzumab-related side effects in­cluded fatigue and fever. Dr. Richardson added that the up­dated premedication prior to elotuzumab in­fusion helped to con­trol in­fusion-related side effects.

There were no treat­ment-related deaths in the study.

Based on these findings, Dr. Richardson and his colleagues rec­om­mended the 10 mg/kg dose of elotuzumab be used in trials going for­ward. “Ten mg/kg of elotuzumab is now the Phase 3 rec­om­mended dose.  Recognizing there are no major dif­fer­ences be­tween the two doses, one there­fore takes the lower dose going for­ward,” ex­plained Dr. Richardson. 

Dr. Richardson added that a large Phase 3 trial with Revlimid and low-dose dexa­meth­a­sone in com­bi­na­tion with elotuzumab in patients with re­lapsed / refractory myeloma patients is antic­i­pated to start in early 2011.

For more in­for­ma­tion about the three elotuzumab stud­ies, please refer to abstract 3023, abstract 1936, and abstract 986 on the American Society of He­ma­tol­ogy annual meeting website.