Preliminary re­­sults from two 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 are resistant (refractory) to pre­vi­ous myeloma treat­ment. The findings were pre­sented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

Elotuzumab is a new drug being devel­oped by Facet Biotech and Bristol-Myers Squibb as a po­ten­tial treat­ment for mul­ti­ple myeloma. It sel­ectively targets pro­teins that are on the surface of myeloma cells, but not healthy cells. When the drug identifies a myeloma cell, it triggers the im­mune sys­tem to kill the can­cer­ous cell.

Elotuzumab In Com­bi­na­tion With Velcade

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

The 28 patients en­rolled in the study re­ceived es­ca­lat­ing doses of elotuzumab (from 2.5 mg/kg to 20 mg/kg) on days 1 and 11 and fixed-dose Velcade (1.3 mg/m²) on days 1, 4, 8, and 11 of a 21-day cycle. Dexa­meth­a­sone was added for patients who progressed early in the trial.

Forty-eight per­cent of the patients responded to the treat­ment, and the median time to dis­ease pro­gres­sion is cur­rently 9.6 months.

“The median time to pro­gres­sion was sig­nif­i­cantly better than what you would ex­pect for this type of patient pop­u­la­tion,” said Dr. Sagar Lonial from the Emory Winship Cancer In­sti­tute during a dis­cus­sion session.

All doses of elotuzumab were well tol­er­ated. The most common treat­ment-related side effects in­cluded fatigue, diarrhea, nausea, 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.

“The com­bi­na­tion of elotuzumab and Velcade is well tol­er­ated,” concluded Dr. Jakubowiak. “The re­sponse rates and time to pro­gres­sion are en­cour­ag­ing.”

Dr. Jakubowiak also said, “These re­­sults in­di­cate possible anti-tumor effects of elotuzumab and Velcade, which are planned to be in­ves­ti­gated in future stud­ies.” The optimal dose of elotuzumab is also yet to be de­ter­mined.

Elotuzumab In Com­bi­na­tion With Revlimid And Dexa­meth­a­sone

Dr. Lonial pre­sented re­­sults from a Phase 1b clin­i­cal trial studying elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone in re­lapsed and re­frac­tory myeloma patients.

The 28 patients en­rolled in the study re­ceived 5, 10, or 20 mg/kg elotuzumab weekly for the first two cycles and then every other week for sub­se­quent cycles. Patients also re­ceived Revlimid (25 mg) on days 1 to 21 of a 21-day cycle and low-dose dexa­meth­a­sone (40 mg) once a week.

The over­all re­sponse rate was 82 per­cent of the patients, with 64 per­cent achieving a partial re­sponse and 18 per­cent achieving a very good partial re­sponse. Notably, the 22 patients who had not been pre­vi­ously treat­ment with Revlimid achieved an over­all re­sponse rate of 95 per­cent (73 per­cent partial re­sponse, 23 per­cent very good partial re­sponse). After 8 months, the median time to dis­ease pro­gres­sion has not yet been reached, as only 39 per­cent of patients have progressed.

In his pre­sen­ta­tion, Dr. Lonial noted, “In the [5 mg and 10 mg groups] of the Phase 1 trial, the planned trial was to end after six months of ther­apy, but based on the very impressive re­sponses we saw, the trial was sub­se­quently amended to allow patients to re­ceive ther­apy beyond six months of ther­apy and are now, in fact, being treated until pro­gres­sion.”

The most common treat­ment-related side effects in­cluded fatigue, diarrhea, con­sti­pa­tion, low red blood cell counts, low white blood cell counts, nausea, muscle spasms, fever, weakness, and short­ness of breath. Two patients in the treat­ment group that re­ceived 20 mg/kg of elotuzumab dis­con­tinued treat­ment due to elotuzumab in­fusion reac­tions.

“Elotuzumab plus Revlimid and low-dose dexa­meth­a­sone has dem­onstrated a man­ageable safety profile,” concluded Dr. Lonial. “Additional [side effects] other than in­fusion reac­tions do not appear to be cumulative or additive com­pared to what we have seen with Revlimid and low-dose dexa­meth­a­sone alone.”

A Phase 2 study with 60 addi­tional patients will fur­ther in­ves­ti­gate ef­fi­cacy and identify the optimal dose of elotuzumab. Dr. Lonial noted that patients en­rolled in the Phase 2 trial are re­quired to take pre-medication to prevent the in­fusion reac­tions that oc­curred in the Phase 1b trial.

For more in­for­ma­tion, please see abstract 8003 (combination with Velcade) and abstract 8020 (combination with Revlimid and dexa­meth­a­sone) on the ASCO meeting website.