Long-Term Responders after Upfront Autologous Hematopoietic Stem Cell Transplant for Multiple Myeloma

Background Autologous stem cell transplantation (autoHCT) is the standard of care for newly-diagnosed MM (NDMM). Although most patients eventually progress, a small proportion of patients achieve a durable response. There are scarce data on this patient population. Methods We conducted a retrospective, single-center, chart review study of patients with NDMM who received upfront autoHCT between 2000-2014. Long-term responders (LTR) were defined as patients with progression-free survival (PFS) of at least eight years following autoHCT. Results We included 1576 patients, 244 (15%) of whom were LTR. Patients in the LTR group were younger than the non-LTR group (median age 58.4 vs. 59.5 years, respectively; p=0.012), less likely to have high-risk cytogenetics (4% vs. 14%; p<0.001), more often had R-ISS stage I disease (43% vs. 34%), and less often had R-ISS stage III disease (3% vs. 10%; p=0.010). The most commonly used induction regimens in the entire cohort were IMiD+dex (30%) and VRD (16%) in both groups (p=0.26). A higher percentage of patients in the LTR group received post-transplant maintenance compared to the non-LTR group (63% vs. 52%; p=0.002) (Table 1). Patients in the LTR group had higher rates of CR at day100 (41% vs. 27%; p<0.001) and at best post-transplant response (70% vs. 37%; p<0.001) compared to the non-LTR group, respectively.The median follow-up time for the entire cohort was 83.7 (range 0.2-262.0) months. Median PFS in the LTR and non-LTR groups was 169.3 months (95% CI 153.1-not reached) and 26.5 months (25.2-28.1), respectively. Median overall survival (OS) was not reached (208.1 months-not reached) and 81.3 months in the non-LTR group (77.5-85.7). Kaplan Meier survival curves for the LTR group are presented in Figure 1.In multivariable analysis, post-transplant maintenance was associated with better PFS [hazard ratio=0.80, p=0.003] and OS [0.84, p=0.037]. Other factors that were associated with better PFS included female gender [0.87, p=0.031] and achieving CR at best post-transplant response [0.62, p<0.001]. In contrast, lambda light chain type [1.23, p=0.002] and high-risk cytogenetics [2.07, p<0.001] were associated with worse PFS. Other factors that were associated with improved OS included female gender [0.83, p=0.017] and achieving CR at best post-transplant response [0.52, p<0.001]. In contrast, lambda light chain type [1.19, p=0.027], high-risk cytogenetics [2.21, p<0.001] and HCT-CI>3 [1.20, p=0.049] were associated with worse OS. Conclusions We identified a subgroup of MM patients with a PFS of ≥8 years after upfront autoHCT, who were younger, had R-ISS stage I disease without high-risk cytogenetics and received post-transplant maintenance. Patients in the LTR group had a median PFS of more than 14 years. These results should be taken into consideration when evaluating the role of upfront autoHCT in light of novel anti-myeloma modalities.