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Elotuzumab Combinations Show Encouraging Results In Relapsed/Refractory Multiple Myeloma (ASH 2010)

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Published: Dec 15, 2010 3:25 pm

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.

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