Long-term survival outcomes of reduced-intensity allogeneic or autologous transplantation in relapsed grade 3 follicular lymphoma

Abstract

Grade-3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade-3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era. A total of 197 patients undergoing first RIC allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naïve patients were excluded. Allo-HCT recipients were younger; more heavily pretreated, and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS) and overall survival (OS) for auto-HCT vs. allo-HCT groups were 4% vs. 27% (p<0.001); 61% vs. 20% (p<0.001); 36% vs. 51% (p=0.07) and 59% vs. 54% (p=0.7), respectively. On multivariate analysis auto-HCT was associated with reduced risk of NRM (RR=0.20; p=0.001). Within the first 11months post-HCT auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; p=0.003) and inferior PFS (RR=3.2; p=0.005). In the first 24 months post-HCT, auto-HCT was associated with improved OS (RR=0.42; p=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; p=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors.

Clinical characteristics and outcomes of relapsed follicular lymphoma after autologous stem cell transplantation in the rituximab era

“…In this study, we retrospectively identified the outcome of 95 patients who relapsed after ASCT at the rituximab era. Although the characteristics and the prognosis were well described at the time of ASCT, 13,16,17,[25][26][27] there is little data available in the literature that describes the survival and prognostic parameters that influence the outcome of R/R transplanted FL patients. One of the aims was to define a historical standard comparator for the development of new approaches.…”

Allogeneic Hematopoietic Cell Transplantation as Curative Therapy for Patients with Non-Hodgkin Lymphoma: Increasingly Successful Application to Older Patients

“…[48] At 5 years, NRM was 27% and OS 54%, indicating that grade 3 histology should not be an exclusion factor for allo-HCT, and that RIC conditioning can offer long-term survival for patients with grade 3 histology.…”

Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure

“…Furthermore, the underlying clinical heterogeneity in FL creates considerable challenges when one is interpreting existing HCT literature. Most HCT studies are small and retrospective, include a mixture of relapsed and refractory disease states, and combine both early and late relapsing patients . The stark survival differences realized by time‐to‐event analyses of FL suggest that more effective therapies are needed for patients with ETF after standard rituximab‐containing chemoimmunotherapy, and it is perhaps this specific high‐risk population for which HCT should be actively pursued.…”

“…Most HCT studies are small and retrospective, include a mixture of relapsed and refractory disease states, and combine both early and late relapsing patients. [6][7][8][9][10][11][12] The stark survival differences realized by timeto-event analyses of FL suggest that more effective therapies are needed for patients with ETF after standard rituximab-containing chemoimmunotherapy, and it is perhaps this specific high-risk population for which HCT should be actively pursued. This approach could prevent the short-and long-term toxicities of HCT in patients who would otherwise expect to have prolonged survival while potentially offsetting the poor prognosis associated with ETF.…”