Drug Combo for Multiple Myeloma Fails in Overall Patient Survival

A randomized Phase 3 clincal trial has concluded that combining bortezomib (Velcade) with pegylated liposomal doxorubicin (PLD) does not show benefit in treating relapsed or refractory multiple myeloma (MM) patients, compared to bortezomib alone.

The data was published in Cancer under the title “Final overall survival results of a randomized trial comparing bortezomib plus pegylated liposomal doxorubicin with bortezomib alone in patients with relapsed or refractory multiple myeloma.”

Although MM patients often respond to initial therapy, the disease eventually relapses and becomes resistant to other treatments. But, with the development of new and more effective drugs, there has been an increase of therapeutic options available for MM patients, particularly for those who relapse after first line therapies.

For the study, researchers led by Dr. Robert Z. Orlowski, interim chair of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, enrolled 645 patients with relapsed or refractory MM who had received one or more lines of treatment, and randomly assigned them to receive either bortezomib plus PLD versus bortezomib alone.

Earlier results from an interim analysis showed that the combination prolonged the median progression-free survival by three months, increased overall survival in 41%, and reduced the risk of disease progression by 45%.

But after a median follow-up of 8.6 months, the median overall survival (OS) was 33 months in the combination group versus 30.8 months in the monotherapy group.

According to the study, researchers believe that the inability to sustain the survival advantage observed in the early interim analysis may have been caused by subsequent lines of therapy received by some patients. In fact, patients in both groups received salvage therapy that included dexamethasone, thalidomide, cyclophosphamide, melphalan, lenalidomide, bortezomib, and doxorubicin. Salvage therapies are drugs of next resort, when others fail.

In an accompanying editorial, Dr. Ajay K. Nooka, assistant professor of hematology and medical oncology at Winship Cancer Institute at the Emory University School of Medicine; and Dr. Sagar Lonial, professor and chair of the department of hematology and medical oncology at Winship, wrote that using two novel agents for MM may lead to better outcomes than combining novel agents with cytotoxic drugs due to synergistic effects.

“Combining cytotoxic agents and even novel agent cytotoxic agent combinations have failed us in the past and continue to fail us now,” they wrote in the editorial. “Although we bid farewell to the routine use of cytotoxic combinations in patients with relapsed myeloma, it is time to realize that not all combination therapies have the same efficacy, and the agents in the combinations do matter.”