The most recent re­­sults of a Phase 2 clin­i­cal trial in­di­cate that elotuzumab in com­bi­na­tion with Revlimid and dexa­meth­a­sone is safe and ef­fec­tive in re­lapsed and re­frac­tory mul­ti­ple myeloma patients.

Dr. Sagar Lonial from the Winship Cancer In­sti­tute at the Emory Uni­ver­sity School of Medicine in Atlanta pre­sented the up­dated Phase 2 re­­sults at the American Society for He­ma­tol­ogy (ASH) annual meeting in San Diego on Monday.

The preceding Phase 1 trial of elotuzumab showed that 82 per­cent of re­lapsed / refractory myeloma patients had a partial re­sponse or better to the drug in com­bi­na­tion with Revlimid (lena­lido­mide) and dexamethasone (Decadron).

Both the Phase 1 re­­sults and initial Phase 2 findings were pre­sented at the American Society of He­ma­tol­ogy annual meeting last De­cem­ber, where Dr. Nikhil Munshi from the Dana-Farber Cancer In­sti­tute was enthusiastic about initial re­­sults from the Phase 2 trial (see re­lated Beacon news). “Elotuzumab in com­bi­na­tion with Revlimid and low-dose dexa­meth­a­sone appears to be very promising,” he said.

Elotuzumab was de­signed to treat myeloma by identifying pro­teins on the surface of myeloma cells and spurring the body's im­mune sys­tem to attack the cancer cells.

Among a num­ber of so-called "monoclonal anti­bodies" being in­ves­ti­gated as po­ten­tial myeloma treat­ments, elotuzumab is the furthest along in the de­vel­op­ment process.

Myeloma re­searchers are ex­cited about the possibility of having mono­clonal anti­bodies as a treat­ment op­tion.  A new class of treat­ments generally lengthens the time physicians can keep an average patient's myeloma under con­trol.

In addi­tion, mono­clonal anti­bodies have made im­por­tant con­tri­bu­tions to the treat­ment of sev­er­al cancers, in­clud­ing the blood cancer lym­phoma.

Elotuzumab initially was tested as a standalone treat­ment for myeloma, but it did not show much ef­fi­cacy when used that way.  Further work in­di­cated, how­ever, that it might work par­tic­u­larly well in com­bi­na­tion with Revlimid.

To date, 73 re­lapsed / refractory myeloma patients have been en­rolled and treated in the on­go­ing Phase 2 trial of elotuzumab.  To par­tic­i­pate in the trial, patients had to have re­ceived be­tween one and three pre­vi­ous myeloma treat­ment regi­mens (the median was two).  A majority of the patients had been pre­vi­ously treated with either Velcade (bor­tez­o­mib) or thalidomide (Thalomid).

Patients who had been pre­vi­ously treated with Revlimid were not permitted to par­tic­i­pate in the trial.

Half of the patients in the trial 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 treat­ment cycles and on days 1 and 15 of sub­se­quent cycles.

In addi­tion, trial par­tic­i­pants re­ceived 25 mg oral Revlimid on days 1 to 21, along with 40 mg dexa­meth­a­sone once per week or 28 mg dexa­meth­a­sone orally plus 8 mg dexa­meth­a­sone by in­tra­venous in­fusion on elotuzumab dosing days.

In order to prevent sev­er­al elotuzumab-related in­fusion reac­tions observed in the Phase 1 trial, patients were given a steroid (prednisone or dexa­meth­a­sone), Benadryl (di­phen­hy­dra­mine), Zantac (ranitidine), and Tylenol (acetaminophen) prior to each elotuzumab in­fusion.

Treatment was dis­con­tinued if patients ex­peri­enced dis­ease pro­gres­sion or severe side effects.

To date, 82 per­cent of patients have had at least a partial re­sponse to the treat­ment regi­men, with 12 per­cent of patients achieving a com­plete re­sponse and 32 per­cent a very good partial re­sponse.

Even more en­cour­ag­ing to re­searchers is the fact that, among patients re­ceiv­ing the 10 mg dose, 92 per­cent had a partial re­sponse or better treat­ment.

Additionally, all patients who had only one prior ther­apy before entering the trial had a partial re­sponse or better to 10 mg/kg in­tra­venous elotuzumab.

The median time to re­sponse was one month.

With a median follow-up of just over 11 months, 22 per­cent of 10 mg/kg treated patients ex­peri­enced dis­ease pro­gres­sion and 30 per­cent of patients in the 20 mg/kg group progressed.

The most common severe side effects were low levels of lym­pho­cytes (a type of white blood cell) in 16 per­cent of patients, low platelet levels (16 per­cent of patients), low white blood cell levels (15 per­cent of patients), and low red blood cell levels (11 per­cent of patients).

In addi­tion, 63 per­cent of patients ex­peri­enced in­fusion reac­tions, the most common of which were nausea (18 per­cent), headache (14 per­cent), fever (14 per­cent), and dizzi­ness (12 per­cent).

The lower, 10mg/kg dose of elotuzumab, is being tested fur­ther in com­bi­na­tion with Revlimid and dexa­meth­a­sone in two large, Phase 3 trials. One study is being con­ducted in newly diag­nosed myeloma patients, the other in re­lapsed / refractory patients.

There also are plans to con­duct a Phase 2 trial of elotuzumab in com­bi­na­tion with Velcade and dexa­methasone as a treat­ment for re­lapsed or re­frac­tory myeloma patients.

For more in­for­ma­tion, see abstract 303 on the ASH meeting website.

Also, as a courtesy to The Beacon’s readers, Dr. Lonial has made the slides of his pre­sen­ta­tion available (pdf) for download and viewing.