Impact of Pretransplant Therapy and Depth of Disease Response before Autologous Transplantation for Multiple Myeloma

Abstract

Patients with multiple myeloma (MM), who are eligible for autologous stem cell transplantation (ASCT), typically receive a finite period of initial therapy prior to ASCT. It is not clear if patients with suboptimal (less than a partial) response to initial therapy benefit from additional alternative therapy with intent to maximize pre-transplant response. We identified 539 patients with MM who had an ASCT after having achieved less than a partial response (PR) to first line induction chemotherapy between 1995 and 2010. These patients were then divided into two groups: those who received additional salvage chemotherapy prior to ASCT (n=324) and those who had no additional salvage chemotherapy immediately prior to ASCT (n=215). Additional pre-transplant chemotherapy resulted in deepening responses in 68% (complete response in 8% and PR in 60%). On multivariate analysis there was no impact of pre-transplant salvage chemotherapy on treatment related mortality (TRM), risk for relapse, progression free or overall survival. In conclusion, for patients achieving a less than PR to initial induction therapy including with novel agent combinations, additional pre-ASCT salvage chemotherapy improved the depth of response and pre-ASCT disease status but was not associated with survival benefit.

Early relapse post autologous transplant is a stronger predictor of survival compared with pretreatment patient factors in the novel agent era: analysis of the Singapore Multiple Myeloma Working Group

“…4,7 Despite these reported associations, additional pretransplant salvage chemotherapy in patients who did not achieve PR post-induction did not improve OS or PFS, even when deeper pretransplant responses were achieved. 15 The different implications of post-induction response reported across studies may reflect differences in study population, underlying disease heterogeneity in myeloma or the weaker predictive value of post-induction response. On the other hand, the depth of posttransplant response appears to be more consistently associated with survival outcomes in prior studies.…”

Limiting early mortality: Do's and don'ts in the management of patients with newly diagnosed multiple myeloma

“…We often encounter patients who despite an ongoing PR on initial regimen had their treatment changed for "suboptimal response." Even though many studies have correlated depth of response with outcomes [112,113], there has not been evidence that replacing an active regimen by another with the objective of obtaining a deeper response will change long-term outcomes [114]. No regimen is free of toxicity.…”

Novel combination approaches for myeloma

“…11 Additional retrospective data from the Center for International Blood and Marrow Transplant Research (CIBMTR) further supports this concept. 12 These observations support using a multi-agent combination therapy with minimal toxicity to achieve the maximal response rapidly, and thereby improve long-term outcomes.…”