Treatment with the experimental agent elotuzumab in combination with Revlimid and dexamethasone demonstrated encouraging efficacy in patients with relapsed/refractory multiple myeloma in a phase 1b/2 study.
Treatment with the experimental agent elotuzumab in combination with Revlimid (lenalidomide) and the steroid dexamethasone demonstrated encouraging efficacy in patients with relapsed/refractory multiple myeloma in an early-stage trial.
The novel mechanism of action of elotuzumab and its safety and efficacy observed in this phase 1b/2 study support the ongoing elotuzumab phase 3 clinical development program in relapsed/refractory myeloma and newly diagnosed myeloma, said lead researcher Paul G. Richardson, from the Dana-Farber Cancer Institute, Boston.
“There is a strong body of evidence to support a dual mechanism of action of this antibody [elotuzumab],” said Richardson. Elotuzumab activates natural killer cells and enables selective cancer cell killing with minimal effects on normal tissue. Clinical activity of elotuzumab in relapsed/refractory multiple myeloma had been established in combination with Revlimid and low-dose dexamethasone in the phase 1b portion of the study, with an overall response rate of 82 percent.
Updated data revealed a median time to disease progression of 33 months for all treatment groups (5, 10, or 20 mg/kg). The randomized phase 2 cohort of the trial randomized 73 patients to receive either 10 or 20 mg/kg of intravenous elotuzumab plus Revlimid and dexamethasone.
Treatment continued until disease progression or unacceptable toxicity. Patients received a premedication regimen before elotuzumab dosing to reduce the risk of infusion reactions. Fifty-five percent of patients received either two or three previous therapies. Sixty percent received prior Velcade (bortezomib) and 62 percent were exposed to thalidomide. One third of patients were refractory to their last myeloma treatment.
The median duration of treatment was 14.8 months. At the data cut-off, 13 patients were still on treatment and 60 patients (82 percent) had discontinued (34 due to disease progression, 12 due to adverse events and 14 for other reasons). The overall response rate was 84 percent.
“All of us in the trial were very struck by the durability of this treatment approach,” Richardson said. “What was particularly exciting was that we saw a remarkable response rate in this relapsed/refractory population, recognizing that they were lenalidomide-naïve.”
A stringent complete response or complete response was observed in 14 percent of patients, a very good partial response was seen in 43 percent and 27 percent had a partial response. The median time to first response was one month and the median duration of response was 20.8 months. The durability of the response was reflected by a median progression-free survival of 28.62 months.
The most common treatment-emergent adverse events were diarrhea (66 percent), muscle spasms (62 percent), fatigue (56 percent), constipation (51 percent), nausea (48 percent) and upper respiratory infection (47 percent), which was similar to the phase 1 experience. The most common grade 3 or 4 adverse events were neutropenia, thrombocytopenia, lymphopenia and anemia.
“It’s important to judge safety in the context of the duration of treatment; patients were on therapy for a number of years,” advised Richardson. The premedication regimen successfully mitigated infusion reactions. The overall rate of infusion reactions was 11 percent.
Based on these promising findings, the Food and Drug Administration granted a breakthrough therapy designation to elotuzumab in combination with Revlimid and dexamethasone as a treatment for patients with multiple myeloma following one or more prior therapies. The designation, which was granted in May 2014, was meant to expedite the development of the promising antibody.
You can read more on breakthrough therapy designations here.
To read more about myeloma, read “From Every Angle.”