European researchers found that the addition of Doxil to Velcade significantly extends the time to disease progression in relapsed / refractory multiple myeloma patients, regardless of age, number of previous therapies, disease stage, and resistance to previous therapy.

However, the addition of Doxil increased the rate of side effects in all patients. Despite the increased rate of side effects, the researchers suggested that Velcade plus Doxil should be considered as an additional standard of care option for myeloma patients, especially those with high-risk disease.

In the last decade, the introduction of novel agents, such as Velcade (bortezomib), Revlimid (lenalidomide), and thalidomide (Thalomid), has dramatically changed the standard of care for multiple myeloma. Research has shown that these new drugs significantly improve treatment outcomes, especially when used in combination therapies.

Doxil (doxorubicin liposomal), which is a new formulation of the anticancer drug doxorubicin (Adriamycin), is approved in the United States for use with Velcade to treat myeloma patients who have received at least one prior therapy other than Velcade.

Recent clinical studies have suggested that the combination of Velcade and Doxil is superior to Velcade alone in relapsed and/or refractory (resistant) myeloma patients.

Based on these results, European researchers aimed to identify which patients would benefit most from the Velcade-Doxil combination. Therefore, they retrospectively analyzed data from a Phase 3 clinical trial that included 646 relapsed and/or refractory myeloma patients. In the trial, participants were randomly assigned to receive treatment with Velcade and Doxil or Velcade alone.

In the retrospective analysis, the researchers analyzed how certain low-risk and high-risk patient groups responded to Velcade plus Doxil therapy compared to Velcade alone.  Specifically, they analyzed responses based on patient characteristics, such as age (less than 65 years of age versus 65 years or older), number of previous lines of therapy (one versus two or more), disease stage (early stage versus later stage), and response to previous line of therapy (non-refractory or refractory).

For all patient groups analyzed, response rates were similar or better with Velcade plus Doxil as compared to Velcade alone.  Response rates were significantly better for patients younger than 65 years of age, those who had received at least two prior therapies, and those who were not refractory to their previous therapy.

Overall, patients treated with Velcade plus Doxil had a significantly longer time to disease progression compared to those who received Velcade alone (9.3 versus 6.5 months).  This held true for all patient groups analyzed, except those with early stage disease, in which there was a trend toward longer time to disease progression, but the difference was not statistically significant.

The median duration of response was also longer, overall, for patients treated with Velcade plus Doxil (10.2 months versus 7.0 months) as well as for all patient groups analyzed.

The addition of Doxil, however, increased the rate of side effects from 64 percent to 80 percent and the rate of serious side effects from 15 percent to 22 percent.

Patient characteristics did not affect the frequency of side effects.  The frequency in patients with high-risk characteristics was comparable to the frequency in the overall patient population.

In addition, the researchers found that the addition of Doxil did not increase the frequency of peripheral neuropathy, a known side effect of Velcade that results in pain and tingling in the arms, hands, legs, and feet.

For more information, please see the study in the journal Clinical Lymphoma, Myeloma & Leukemia (abstract).