Elotuzumab in com­bi­na­tion with Revlimid and dexa­meth­a­sone con­tinues to show prom­ise in re­lapsed and re­frac­tory myeloma patients, ac­cord­ing to up­dated re­­sults from an on­go­ing Phase 2 clin­i­cal trial.

Response rates con­tinued to be high, par­tic­u­larly among study par­tic­i­pants re­ceiv­ing the lower elotuzumab dose.  In addi­tion, the rate of severe side effects remained low.

Dr. Philippe Moreau from the Uni­ver­sity Hospital in Nantes, France, pre­sented the re­­sults last Monday at the 48th annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“This com­bi­na­tion seems to be highly active in re­lapsed and re­frac­tory myeloma patients,” said Dr. Andrzej Jakubowiak, the director of the myeloma pro­gram at the Uni­ver­sity of Chicago, during a pre­sen­ta­tion accompanying Dr. Moreau’s talk. “The data for this patient pop­u­la­tion is very convincing to me,” he added.

Elotuzumab ^[1], which is being devel­oped by Bristol-Myers Squibb (NYSE: BMY), belongs to a class of drugs called mono­clonal anti­bodies. Monoclonal anti­bodies work by identifying pro­teins on the surface of myeloma cells and signaling for the im­mune sys­tem to destroy the cancer cells.  Other com­pounds in this class of drugs in­clude daratumumab ^[2] and siltuximab ^[3], which are in earlier phases of clin­i­cal de­vel­op­ment than elotuzumab.

The Phase 2 elotuzumab study in­cluded 73 re­lapsed / refractory myeloma patients with a median age of 63 years.

All patients were re­quired to have had one to three pre­vi­ous lines of ther­apy. Fifty-five per­cent of patients had re­ceived at least two prior ther­a­pies. Sixty per­cent of patients had re­ceived prior treat­ment with Velcade ^[4] (bor­tez­o­mib), and 62 per­cent had re­ceived prior treat­ment with thalidomide ^[5] (Thalomid). Patients who pre­vi­ously had re­ceived Revlimid ^[6] (lena­lido­mide) were not eli­gible to par­tic­i­pate in the trial.

Thirty-six patients re­ceived 10 mg/kg of in­tra­venous elotuzumab on days 1, 8, 15, and 22 of the first two 28-day treat­ment cycles, and on days 1 and 15 of sub­se­quent cycles. The remaining 37 patients re­ceived 20 mg/kg of in­tra­venous elotuzumab on the same days.

The patients also re­ceived 25 mg of Revlimid on days 1 to 21, along with 40 mg of dexamethasone ^[7] (Decadron) orally once per week or 28 mg dexa­meth­a­sone orally plus 8 mg dexa­metha­sone by in­tra­venous in­fusion on elotuzumab dosing days.

The over­all re­sponse rate was 84 per­cent for all patients.

Preliminary re­­sults of the study pre­sented at the American Society of He­ma­tol­ogy’s annual meeting in De­cem­ber in­di­cated that the lower dose seems to be more ef­fec­tive than the higher dose (see re­lated Beacon ^[8] news).

Dr. Moreau con­firmed that trend during his pre­sen­ta­tion on Monday: The over­all re­sponse rate con­tinued to be higher among patients who re­ceived 10 mg/kg of elotuzumab (92 per­cent), com­pared to patients who re­ceived 20 mg/kg of elotuzumab (76 per­cent).

Among patients treated with just a single pre­vi­ous line of ther­apy, all patients who re­ceived 10 mg/kg and 82 per­cent of patients who re­ceived 20 mg/kg of elotuzumab responded.

“[These re­­sults] in­di­cate that this com­bi­na­tion could also be ef­fec­tive in front­line treat­ment,” said Dr. Moreau.

Among patients who re­ceived two or more prior lines of ther­apy, the re­sponse rates remained high for both dosing groups (85 per­cent and 70 per­cent, re­spec­tively).

According to Dr. Moreau, the re­sponse rate was also high among patients with high-risk chromosomal ab­nor­mal­i­ties. However, he pointed out that the share of patients with high-risk chromosomal ab­nor­mal­i­ties was small in this study (14 per­cent), so re­­sults need to be interpreted cautiously.

Dr. Moreau also mentioned that patients showed a rapid re­sponse to treat­ment. The median time to re­sponse was one month, and the median time to best re­sponse was 2.5 months.

According to Dr. Moreau, the high re­sponse rate was also asso­ci­ated with a pro­longed re­sponse duration. After a median follow-up time of 17.2 months, the median pro­gres­sion-free sur­vival has not been reached yet for patients in the 10 mg/kg treat­ment group and was 19 months for patients in the 20 mg/kg treat­ment group.

“These data are really en­cour­ag­ing when com­pared to those achieved with Revlimid and high-dose dexa­meth­a­sone,” said Dr. Moreau.

The median pro­gres­sion-free sur­vival for patients with high-risk chromosomal ab­nor­mal­i­ties was nine months, which Dr. Moreau also described as en­cour­ag­ing.

According to Dr. Moreau, the treat­ment was well tol­er­ated at both dose levels. The most common severe side effects were blood-related and in­cluded low red blood cell counts, low white blood cell counts, and low platelet counts.

Dr. Moreau pointed out that only one patient devel­oped in­fusion-site reac­tions, a common side effect of mono­clonal anti­bodies.

The re­searchers observed four cases of sec­ond cancer among the trial par­tic­i­pants.

The main reason for treat­ment dis­con­tinu­a­tion was dis­ease pro­gres­sion.

Two Phase 3 trials of elotuzumab in com­bi­na­tion with Revlimid and dexa­meth­a­sone have been ini­ti­ated in both newly diag­nosed and re­lapsed and re­frac­tory myeloma patients.

One of these trials will in­clude 750 newly diag­nosed myeloma patients who are in­eli­gible for stem cell trans­plan­ta­tion.  The other one will in­clude 640 re­lapsed and re­frac­tory myeloma patients who have re­ceived be­tween one to three prior ther­a­pies. The lower dose from the Phase 2 trial (10 mg/kg) will be used in the Phase 3 trials.

Elotuzumab is also being in­ves­ti­gated in a Phase 2 trial in com­bi­na­tion with Velcade and dexa­meth­a­sone in re­lapsed and re­frac­tory myeloma patients.  This trial will in­clude 150 re­lapsed and re­frac­tory myeloma patients.

Patients will be eval­u­ated for re­sponse in all three trials.  Progression-free sur­vival and over­all sur­vival will also be tracked.

For more in­for­ma­tion on the Phase 2 trial re­­sults, please see abstract 8020 ^[9]. For a description of the new trials, please see abstracts TPS8112 ^[10], TPS8113 ^[11], and TPS8114 ^[12] on the ASCO ^[13] meeting website.