Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma

Abstract

Background: Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of riskfactors (RFs) for survival after ASCT. Methods: In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HLpatients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resultingprognostic score was then validated in an independent clinical sample (part II).Results: In part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-upof 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazardratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse≤3 months, ECOG performancestatus≥1, bulk≥5 cm and inadequate response to salvage chemotherapy [ <0.0001). Validation in an independent sample of 389 patients treated indifferent clinical settings with evaluation of response to salvage therapy by functional imaging instead of CT confirmed the excellentdiscrimination of risk groups and significant prognostication of PFS and overall survival (OS) after ASCT (HR=1.70 andHR=1.63, respectively; P<0.0001).Conclusions: Based on this large study (n=1045), precise and valid risk prognostication in HL patients undergoing ASCT canbe achieved with five easily available clinical RFs. The proposed prognostic score hence allows reliable stratification of patientsfor innovative therapeutic approaches in clinical practice and future trials.