Progression-free survival at 2 years post-autologous transplant: a surrogate end point for overall survival in follicular lymphoma

Abstract

Overall survival (OS) is the gold-standard end point for studies evaluating autologous stem cell transplantation (ASCT) in follicular lymphoma (FL), but assessment may be elusive due to the lengthy disease course. We analyzed the validity of two earlier end points, proposed in the setting of first-line chemo-/immunotherapy, as surrogates for OSprogression-free survival (PFS) status at 24months (PFS24) and complete response at 30months (CR30) post-ASCT. We also have investigated the clinical features of patients with early progression after ASCT. Data were available for 626 chemosensitive FL patients who received ASCT between 1989 and 2007. Median follow-up was 12.2years from ASCT. In the PFS24 analysis, 153 (24%) patients progressed within 24months and 447 were alive and progression-free at 24months post-ASCT (26 who died without disease progressions within 24months were excluded). Early progression was associated with shorter OS (hazard ratio [HR], 6.8; P=0.00001). In the subgroup of patients who received an ASCT in the setting or relapse after being exposed to rituximab, the HR was 11.3 (95% CI, 3.9-30.2; P<0.00001). In the CR30 analysis, 183 of 596 (31%) response-evaluable patients progressed/died with 30months post-ASCT. The absence of CR30 was associated with shorter OS (HR, 7.8; P<0.00001), including in patients with prior rituximab (HR, 8.2). PFS24 and CR30 post-ASCT are associated with poor outcomes and should be primary end points. Further research is needed to identify this population to be offered alternative treatments.