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 OS—progression‐free survival (PFS) status at 24 months (PFS24) and complete response at 30 months (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 12.2 years from ASCT. In the PFS24 analysis, 153 (24%) patients progressed within 24 months and 447 were alive and progression‐free at 24 months post‐ASCT (26 who died without disease progressions within 24 months 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 30 months 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.
Highlights
Follicular lymphoma (FL) is the most common of indolent lymphoma
According to GELTAMO guidelines, complete response (CR) was defined as the disappearance of all clinical evidence of disease, with normalization of X-rays, CT scans, and laboratory values that had been abnormal before therapy; partial response (PR) was defined as a ≥50% reduction in measurable disease for ≥1 month; resistant/refractory disease was defined as lymphoma that progressed during initial combination chemotherapy or a response of less than PR to salvage therapy [20, 21]
This report represents the first analysis of chemosensitive FL patients receiving Autologous stem cell transplantation (ASCT) that suggests that PFS24 could be a valid surrogate and primary end points for overall survival (OS) in this setting
Summary
Follicular lymphoma (FL) is the most common of indolent lymphoma. The combination of conventional chemotherapy, radiotherapy, anti-CD20 immunotherapy, and stem cell transplantation has contributed to modifying the natural history of FL [1,2,3]. Demonstration of an OS benefit requires a long observation period and large numbers of patients [5, 6] For this reason, the OS assessment to evaluate the efficacy of the different therapeutic alternatives in FL can be elusive. In the era of novel targeted therapeutics that offers clinical benefit for long period of times, PFS may as well have fleeting relevance [9, 10]. This extended PFS prolongs the duration of clinical trials and limits the ability to approve new effective therapeutic options against FL. The identification of alternative or surrogate end points that are measured earlier but can reliably predict PFS treatment effect has been a critical need for decades
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