Continuous therapy improves multiple myeloma outcomes

By Shreeya Nanda, Senior medwireNews Reporter

Patients with newly diagnosed multiple myeloma receive significant progression-free and overall survival (PFS, OS) benefits from continuous treatment compared with fixed-duration therapy, suggests a pooled analysis.

The researchers evaluated both PFS1 and PFS2 – defined as the time to first progression or death and time to second progression or death, respectively – and found that continuous therapy significantly extended both endpoints.

“Our findings suggest that most of the PFS1 advantage associated with [continuous therapy] up front is maintained after first relapse and that [continuous therapy] does not induce a significant chemotherapy resistance”, they say.

This pooled analysis included individual patient data from three phase III trials in which multiple myeloma patients were randomly assigned to receive continuous or fixed-duration therapy with first-line novel agents – thalidomide, lenalidomide or bortezomib. The fixed-duration and continuous therapy protocols both involved upfront induction or consolidation therapy for an average of 1 year, but continuous therapy additionally included a minimum 2 years of maintenance.

Among the 827 participants alive and progression free a year after treatment assignment, considered the intent-to-treat population, median PFS1 was 32 months for the 417 patients who received continuous therapy. This was significantly longer than the 16 months for the 410 participants given fixed-duration therapy, equating to a hazard ratio (HR) for first progression or death of 0.47.

PFS2 was similarly significantly longer in the continuous than in the fixed-duration group, at a median of 55 versus 40 months, with a HR for second progression or death of 0.61.

Moreover, patients given continuous therapy had a significantly lower risk of death than those treated with the fixed-duration protocol, with 4-year OS rates of 69% versus 60% and a HR of 0.69.

Researcher Antonio Palumbo (University of Torino, Italy) and team report that after the induction or consolidation phase, 12% of patients in the continuous therapy group and 2% of those given fixed-duration therapy discontinued treatment as a result of adverse events. But “[t]his difference did not negatively affect efficacy, confirming the overall benefit of [continuous therapy]”, they write.

Approximately 90% of patients in either group who experienced relapse received second-line treatment, say the study authors, which suggests that continuous therapy does not “induce significant long-term toxicity” that precludes patients from receiving treatment after relapse.

They conclude in the Journal of Clinical Oncology: “Future studies evaluating other new, effective antimyeloma agents with… different mechanisms of action (such as new-generation proteasome inhibitors and immunomodulatory agents or monoclonal antibodies) will shed further light on the role of [continuous therapy].”

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