Depth of Response with Stem Cell Transplantation and Outcome for Multiple Myeloma in the Era of Novel Agents.

It is generally believed that a ‘deeper’ response in multiple myeloma is associated with an improved outcome, including time to progression (TTP) as well as overall survival. Before the advent of novel agents such as IMiDs or bortezomib, complete responses (CR) were rare in the absence of stem cell transplantation (ASCT). In that era, the depth of response achieved before ASCT tended to be dwarfed by the impact of the conditioning used for stem cell transplant. Hence, the time to progression in patients achieving CR before ASCT was not different from those who achieved CR after ASCT. With novel agents, CR rates are higher and again raises the question of whether patients who achieve CR before ASCT benefit from consolidation with ASCT. The purpose of this analysis was to determine whether CR achieved before ASCT still benefit when consolidated with ASCT

After approval from the Institutional Review Board at Mayo Clinic Rochester, the transplant dysproteinemia database was searched for all patients treated with novel agents and patients who achieved CR before or after ASCT were identified. In addition, we identified patients with IMiDs induction therapy and achieved CR but did not proceed with ASCT. Relevant demographic, clinical and laboratory characteristics were determined at the time of ASCT. Comparisons between groups were performed with non-parametric tests. Overall survival and TTP were determined from the time of ASCT using the Kaplan-Meier method.

A total of 354 patients who underwent ASCT within a year from diagnosis of multiple myeloma were identified. Of these, 24 achieved CR before proceeding to ASCT while another 100 patients achieved CR after ASCT. There were no differences between the two cohorts with respect to age (58 vs 57.5 yr, p=0.14), gender, number of treatment regimens (1 vs 1, p=0.83), time to ASCT (6.5 vs 6.3 months, p=0.80), b₂M (2.41 vs 2.26, p=0.58) and ISS (p=0.23). Patients who achieved CR before ASCT had a lower plasma cell burden (1.0 vs 5.0%, p<0.0001) and lower labeling index (0 vs 0, p=0.0007). Aneuploidy was present in none of the patients with CR before transplant compared to 10% in patients who achieved CR after ASCT (p=0.11). The median TTP for patients with CR before ASCT has not been reached (71% at 70 months) compared to 30 months for patients who achieved CR after ASCT (p=0.07). After a median follow up of 70 months, 21 of 24 patients (88%) with CR before transplant are alive compared to 76 of 100 patients with CR after ASCT (p=0.44). In contrast, for patients who achieved CR with IMiDs but did not proceed with ASCT, 55% have not progressed at 51 months and 71.7% are alive at 51 months (Gay et al ASH, 2009).

Our results suggest that patients who achieve CR before ASCT benefit from high-dose therapy and experience prolonged TTP without the need for maintenance therapy. ASCT after achieving CR can result in a deeper response with improvement in disease free and overall survival.

Lacy:celgene: Research Funding. Gertz:celgene: Honoraria; genzyme: Honoraria; millenium: Honoraria; amgen: Honoraria.