New 4-Drug Combo Leads to Promising Responses in Multiple Myeloma

Patients with multiple myeloma who didn’t respond to previous treatment showed encouraging responses when they were given the drug elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone (elo-PVD, for short), according to a phase 2 clinical trial.

Clinical trials are designed to test the safety and effectiveness of new drugs. Phase 2 clinical trials are carried out with a fairly small number of patients, and tell doctors more about how safe a cancer treatment is and how well it works.

To participate in this trial, patients had to have relapsed or refractory multiple myeloma and at least 1 previous line of treatment. The term “relapsed” refers to patients whose cancer reappeared or grew again after a period of remission, and “refractory” is used to describe a person whose cancer did not respond to treatment (meaning that their cancer cells continued to grow), or whose response to treatment did not last very long.

A total of 48 patients participated in the trial. Elotuzumab was given once a week for the first two 28-day cycles, and then every other week. Pomalidomide was given daily on days 1 through 21, bortezomib was given on days 1, 8, and 15, and dexamethasone was given once a week.

All patients had already received treatment with lenalidomide and either bortezomib or carfilzomib, and were refractory to their last line of therapy. Other therapies patients had received were autologous stem-cell transplant in 48%, pomalidomide in 33%, daratumumab in 25%, and isatuximab in 4%.

When the researchers collected these data, 16 patients were still participating in the study: 27 patients quit the study because their cancer progressed, 3 dropped out because of side effects, 1 patient had a transplant, and 1 patient was lost to follow-up.

The researchers looked at response rates in 46 of the patients (2 did not meet the criteria for evaluation), and they saw 16 partial responses, 10 very good partial responses, and 2 complete responses. Partial response means there was a decrease in the amount of cancer in the body, very good partial response means the amount of cancer decreased even more, and complete response means the researchers could not find any more cancer in the body.

In the 19 patients who had received only 1 previous line of therapy, response rates were even higher.

The treatment was well-tolerated, and side effects were manageable. Grade 3 or worse hematologic (relating to the blood or bone marrow) side effects were anemia in 10% of patients, neutropenia in 29%, and thrombocytopenia in 15%. Grade 3 side effects are severe or medically significant, but not immediately life-threatening.

Other common grade 3 or worse side effects included lung infection in 27% of patients and hypophosphatemia in 15%. More non-hematologic side effects of any grade were fatigue, upper respiratory tract infection, diarrhea, constipation, hyperglycemia, and sensory neuropathy. There were 2 deaths, possibly related to sepsis or pneumonia.

According to Dr. Andrew Yee, one of the lead investigators on the study, any infectious complications were manageable, and “likely reflect the real-world impact of using a 4-drug combination in a heavily pretreated patient population.”

“As upfront and subsequent regimens are increasingly more intensive, newer combinations are necessary to address more challenging-to-treat relapses,” said Dr. Yee. “Elo-PVD is one promising example of such a combination.”