No Association Between Response Rates and Survival in Newly Diagnosed Multiple Myeloma

There was no association between conventional response outcomes, such as complete response (CR) or very good partial response (VGPR), and survival in patients with newly diagnosed multiple myeloma, according to the results of a meta-regression analysis published recently in the European Journal of Hematology.

“We explored the relationship between response to initial treatment and survival in patients with newly diagnosed multiple myeloma, based on data from 63 randomized clinical trials,” wrote researcher Maria Mainou, of the clinical research and evidence-based medicine unit at Aristotle University of Thessaloniki, Greece, and colleagues. “Meta-regression analyses failed to demonstrate any association between CR or (CR or VGPR) with either overall survival or progression-free survival both in patients receiving autologous stem cell transplant [ASCT] and in non-ASCT patients.”

However, Mainou noted that “the certainty in this lack of association is low, mainly due to increased heterogeneity and high overall risk of bias” in the results.

According to the study, the outcomes of CR and VGPR are commonly used to evaluate the efficacy of treatments for myeloma. However, there are conflicting data on whether or not CR is associated with longer overall and progression-free survival, and the role of transplant in survival outcomes. Instead, newer trials have suggested that the use of minimal residual disease (MRD) status may be a valid surrogate outcomes for survival in patients with myeloma who achieved CR.

With this meta-analysis, Mainou and colleagues explored the association between response to initial treatment and survival outcomes in patients with newly diagnosed myeloma. They looked at studies with response outcomes including CR, and combined CR and VGPR. Survival outcomes included overall survival and progression-free survival. The meta-regression analyses included 63 trials.

Based on the data from these trials, the researchers found no association between overall survival and CR among patients without transplant, in patients who underwent transplant, and in trials comparing transplant with non-transplant patients. Overall survival did not correlate with the combined outcomes of CR and VGPR.

Similarly, an analysis of trials of patient who did not undergo transplant showed no correlation of progression-free survival with CR or with combined CR and VGPR.

“The lack of association between response rates and hard clinical outcomes raises concerns about fast track approval of new drugs, based on results from trials utilizing solely these surrogate markers,” the researchers wrote. “Given the limitations of CR or VGPR to accurately reflect survival in patients with newly diagnosed multiple myeloma, prospective studies should include MRD in addition to conventional response outcomes.”