Continuous Therapy Delayed Progression in Newly Diagnosed Myeloma

The use of continuous therapy resulted in significant delays in first progression (PFS1) and second progression (PFS2) and an improvement in overall survival (OS) compared with fixed-duration therapy in patients with newly diagnosed multiple myeloma, according to the results of a pooled analysis published in the Journal of Clinical Oncology.

According to the study, there is concern that patients with myeloma who relapse on continuous therapy may develop drug resistance to at least their initial therapy.

“Our results indicate that continuous therapy provides a clinically relevant improvement in median PFS1 and PFS2 of approximately 1 year and an OS improvement of approximately 10% in patients with newly diagnosed multiple myeloma,” wrote study author Antonio Palumbo, MD, chief of the myeloma unit at the University of Torino in Italy, and colleagues. “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.”

In this study, Palumbo and colleagues pooled data from three phase III randomized trials that included 604 patients assigned to a continuous therapy vs fixed-duration therapy schedule. They evaluated time to PFS1, time to PFS2, and OS.

“The three trials included in this pooled analysis evaluated different types of continuous therapy and different patient populations, eligible and ineligible for transplantation,” the researchers clarified in their discussion. “This variability was managed through a careful adjustment, including the trial effect and the induction treatment, and with a sensitivity analysis by removing one trial at a time.”

With a median follow-up of 52 months, patients assigned to continuous therapy had significant improvements in all three endpoints compared with patients assigned to fixed-duration therapy.

The median time to PFS1 was 32 months for patients on continuous therapy compared with 16 months for patients on fixed-duration therapy (hazard ratio [HR] = 0.47 [95% confidence interval (CI), 0.40–0.56]; P < .001) and the median time to PFS2 was 55 months compared with 40 months (HR = 0.61 [95% CI, 0.50–0.75]; P < .001).

“The benefit of continuous therapy vs fixed-duration therapy was evident in all of the subgroups according to trial and induction/consolidation treatment (P = .861 for interaction) and in most of the analyzed subgroups according to baseline features, with a possible weaker effect on women,” the researchers wrote.

In addition, the median 4-year overall survival was 69% for continuous therapy compared with 60% for fixed-duration therapy (HR = 0.69 [95% CI, 0.54–0.88]; P < .003).

“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,” the researchers wrote.