Elotuzumab plus len-dex extends remissions of multiple myeloma

Adding the investigational monoclonal antibody elotuzumab to a standard regimen for early relapsed/refractory multiple myeloma extended the duration of remissions by a mean of 5 months.

The combination of elotuzumab (elo), lenalidomide (len), and dexamethasone (dex) was associated with a 30% reduction in the risk of disease progression or death compared with len/dex alone, and the benefit of the drug was also seen, although to a lesser degree, in patients with high-risk disease mutations, reported Dr. Sagar Lonial of the Winship Cancer Institute of Emory University, Atlanta.

“We were certainly excited about the fact that there is such a big difference in progression-free survival between the two arms,” he said at a briefing on studies to be presented at the annual meeting of the American Society of Clinical Oncology.

“Patients who received elotuzumab had a longer duration of remission and had a higher overall response rate, and this improvement in clinical parameters occurred without a significant increase in adverse events or toxicity,” he added.

Dr. Julie M. Vose, ASCO president-elect, who comoderated the briefing, said that “although we have had monoclonal antibodies in a number of other malignancies for years, this truly is the first one for myeloma.”

Dr. Lonial reported interim results from ELOQUENT-2, a phase III study comparing the efficacy and safety of the elo/len/dex combination vs. len/dex alone in 646 patients with relapsed/refractory multiple myeloma who had received one, two, or three prior lines of therapy and whose disease was not resistant to len/dex.

The patients were randomized to receive either oral len/dex on a standard schedule, or oral lenalidomide plus oral dexamethasone on weeks when there was no elotuzumab infusion, with both oral and intravenous dexamethasone delivered on weeks when the antibody was delivered by solutional infusion. The regimens were delivered in 28-day cycles until disease progression or unacceptable toxicities occurred.

At 24 months median follow-up, the mean progression-free survival (PFS) for patients on elo/len/dex was 19.4 months, compared with 14.9 months for len/dex alone (P = .0004). One-year PFS rates were 68% for elo/len/dex, compared with 57% for len/dex. Two-year PFS rates were 41% vs. 27%, respectively.

The overall response rate with the antibody-containing combination was 79% compared with 66% for len/dex alone (P = .0002). Dr. Lonial noted that the antibody-containing combination was effective both in patients with average risk, and in those with the high risk cytogenetic abnormalities, including the 17p deletion and the t(4;14) chromosomal translocation, although the response was not as robust in these patients.

A total of 210 patients died during follow-up, 94 who had been treated with elo/len/dex, and 116 who had been treated with len/dex.

Grade 3 or 4 adverse events occurring in 15% or more of patients included neutropenia in 25% of patients on elo/len/dex, and 33% of patients on len/dex, and anemia, which occurred in 15% and 16% of patients, respectively. In all, 10% of patients in the elotuzumab arm had mild infusion reactions after the first few doses.

Based on data from earlier trials, the Food and Drug Administration has granted elotuzumab breakthrough designation for treatment of multiple myeloma that has relapsed or is refractory to at least one prior line of therapy. Breakthrough status entitles the manufacturer to an expedited review of the drug.

Adding the investigational monoclonal antibody elotuzumab to a standard regimen for early relapsed/refractory multiple myeloma extended the duration of remissions by a mean of 5 months.

The combination of elotuzumab (elo), lenalidomide (len), and dexamethasone (dex) was associated with a 30% reduction in the risk of disease progression or death compared with len/dex alone, and the benefit of the drug was also seen, although to a lesser degree, in patients with high-risk disease mutations, reported Dr. Sagar Lonial of the Winship Cancer Institute of Emory University, Atlanta.

“We were certainly excited about the fact that there is such a big difference in progression-free survival between the two arms,” he said at a briefing on studies to be presented at the annual meeting of the American Society of Clinical Oncology.

“Patients who received elotuzumab had a longer duration of remission and had a higher overall response rate, and this improvement in clinical parameters occurred without a significant increase in adverse events or toxicity,” he added.

Dr. Julie M. Vose, ASCO president-elect, who comoderated the briefing, said that “although we have had monoclonal antibodies in a number of other malignancies for years, this truly is the first one for myeloma.”

Dr. Lonial reported interim results from ELOQUENT-2, a phase III study comparing the efficacy and safety of the elo/len/dex combination vs. len/dex alone in 646 patients with relapsed/refractory multiple myeloma who had received one, two, or three prior lines of therapy and whose disease was not resistant to len/dex.

The patients were randomized to receive either oral len/dex on a standard schedule, or oral lenalidomide plus oral dexamethasone on weeks when there was no elotuzumab infusion, with both oral and intravenous dexamethasone delivered on weeks when the antibody was delivered by solutional infusion. The regimens were delivered in 28-day cycles until disease progression or unacceptable toxicities occurred.

At 24 months median follow-up, the mean progression-free survival (PFS) for patients on elo/len/dex was 19.4 months, compared with 14.9 months for len/dex alone (P = .0004). One-year PFS rates were 68% for elo/len/dex, compared with 57% for len/dex. Two-year PFS rates were 41% vs. 27%, respectively.

The overall response rate with the antibody-containing combination was 79% compared with 66% for len/dex alone (P = .0002). Dr. Lonial noted that the antibody-containing combination was effective both in patients with average risk, and in those with the high risk cytogenetic abnormalities, including the 17p deletion and the t(4;14) chromosomal translocation, although the response was not as robust in these patients.

A total of 210 patients died during follow-up, 94 who had been treated with elo/len/dex, and 116 who had been treated with len/dex.

Grade 3 or 4 adverse events occurring in 15% or more of patients included neutropenia in 25% of patients on elo/len/dex, and 33% of patients on len/dex, and anemia, which occurred in 15% and 16% of patients, respectively. In all, 10% of patients in the elotuzumab arm had mild infusion reactions after the first few doses.

Based on data from earlier trials, the Food and Drug Administration has granted elotuzumab breakthrough designation for treatment of multiple myeloma that has relapsed or is refractory to at least one prior line of therapy. Breakthrough status entitles the manufacturer to an expedited review of the drug.

Adding the investigational monoclonal antibody elotuzumab to a standard regimen for early relapsed/refractory multiple myeloma extended the duration of remissions by a mean of 5 months.

The combination of elotuzumab (elo), lenalidomide (len), and dexamethasone (dex) was associated with a 30% reduction in the risk of disease progression or death compared with len/dex alone, and the benefit of the drug was also seen, although to a lesser degree, in patients with high-risk disease mutations, reported Dr. Sagar Lonial of the Winship Cancer Institute of Emory University, Atlanta.

“We were certainly excited about the fact that there is such a big difference in progression-free survival between the two arms,” he said at a briefing on studies to be presented at the annual meeting of the American Society of Clinical Oncology.

“Patients who received elotuzumab had a longer duration of remission and had a higher overall response rate, and this improvement in clinical parameters occurred without a significant increase in adverse events or toxicity,” he added.

Dr. Julie M. Vose, ASCO president-elect, who comoderated the briefing, said that “although we have had monoclonal antibodies in a number of other malignancies for years, this truly is the first one for myeloma.”

Dr. Lonial reported interim results from ELOQUENT-2, a phase III study comparing the efficacy and safety of the elo/len/dex combination vs. len/dex alone in 646 patients with relapsed/refractory multiple myeloma who had received one, two, or three prior lines of therapy and whose disease was not resistant to len/dex.

The patients were randomized to receive either oral len/dex on a standard schedule, or oral lenalidomide plus oral dexamethasone on weeks when there was no elotuzumab infusion, with both oral and intravenous dexamethasone delivered on weeks when the antibody was delivered by solutional infusion. The regimens were delivered in 28-day cycles until disease progression or unacceptable toxicities occurred.

At 24 months median follow-up, the mean progression-free survival (PFS) for patients on elo/len/dex was 19.4 months, compared with 14.9 months for len/dex alone (P = .0004). One-year PFS rates were 68% for elo/len/dex, compared with 57% for len/dex. Two-year PFS rates were 41% vs. 27%, respectively.

The overall response rate with the antibody-containing combination was 79% compared with 66% for len/dex alone (P = .0002). Dr. Lonial noted that the antibody-containing combination was effective both in patients with average risk, and in those with the high risk cytogenetic abnormalities, including the 17p deletion and the t(4;14) chromosomal translocation, although the response was not as robust in these patients.

A total of 210 patients died during follow-up, 94 who had been treated with elo/len/dex, and 116 who had been treated with len/dex.

Grade 3 or 4 adverse events occurring in 15% or more of patients included neutropenia in 25% of patients on elo/len/dex, and 33% of patients on len/dex, and anemia, which occurred in 15% and 16% of patients, respectively. In all, 10% of patients in the elotuzumab arm had mild infusion reactions after the first few doses.

Based on data from earlier trials, the Food and Drug Administration has granted elotuzumab breakthrough designation for treatment of multiple myeloma that has relapsed or is refractory to at least one prior line of therapy. Breakthrough status entitles the manufacturer to an expedited review of the drug.