Early Relapse Linked With Poor Post-Transplant Survival in Myeloma

Early relapse after autologous stem cell transplantation was linked with worse overall survival in patients with multiple myeloma who received novel agent–based induction therapy prior to transplant, according to the results of a small Singapore study.

However, a majority of patients who had novel agent–based induction therapy had very good partial response post-transplant, the study found. The results were published in Bone Marrow Transplantation.

“Of note, among the patients who relapsed within a year, almost half had initially achieved very good partial response post-transplant,” wrote S.Y. Ong, of Singapore General Hospital, and colleagues. “Patients who suffered early relapse have a dismal post-relapse survival of 11 months despite salvage therapy, and present an unmet therapeutic challenge.”

According to the study, the incidence of myeloma is increasing rapidly in Singapore; there are little data on the effect of novel myeloma agents, such as bortezomib, thalidomide, and lenalidomide, on transplant outcomes among Asian patients.

Ong and colleagues conducted a retrospective study examining the outcomes of 215 patients with multiple myeloma treated with upfront transplant in Singapore between 2000 and 2014. Seventy-six percent of these patients received therapy with a novel agent.

Sixty-five percent of patients who received novel agent induction therapy achieved very good partial response compared with only 31% of patients who did not get novel agents (P < .001). These improved responses translated into significantly improved overall survival for patients treated with novel agents (97 vs 58 months; P = .023). However, no significant difference in progression-free survival (PFS) was found.

“An explanation for an improved overall survival without significantly different PFS in the novel agent group is that more than 90% received effective therapy after progression (eg, lenalidomide which has significant activity in patients refractory to thalidomide), while only 15% of patients in the non–novel agent group received a novel agent (mainly thalidomide) after relapse,” the researchers wrote.

Data indicated that those patients who had relapse within 12 months of transplant had significantly worse overall survival, with a median of 16 months compared with 122 months for those who did not have early relapse (P < .001). Early relapse was associated with poor overall survival in patients who received novel agents (hazard ratio [HR], 13.7) and those who did not (HR, 5.1).

“Although maximizing response is an important endpoint, 18% of patients relapse early, of which nearly half [had] very good partial response or better post-transplant,” the researchers wrote. “Early relapse appears as an important treatment-related factor independent of, and more significant than, higher International Staging System stage or high-risk FISH markers in determining survival in our series. Therefore, more effective risk stratification markers are needed to identify patients before early relapse, and novel management strategies are needed to prevent early relapse.”