Risk factors and a prognostic score for survival after autologous stem cell transplantation for relapsed or refractory Hodgkin lymphoma
Menée à partir des données de 9 essais portant sur 656 patients atteints d'un lymphome hodgkinien réfractaire ou récidivant traité entre 1993 et 2013 (durée médiane de suivi : 60 mois) puis validée sur 389 patients complémentaires, cette étude évalue la performance d'un système de score, basé sur cinq facteurs clinico-pathologiques associés à la survie (stade IV, délai avant récidive inférieur ou égal à 3 mois, ...), pour identifier les patients pouvant bénéficier de traitements innovants après une greffe autologue de cellules souches
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 risk factors for survival after ASCT.
Methods : In this multinational prognostic multivariable modeling study, 23 potential risk factors (RF) were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic 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-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy (<PR by CT) as significant and non-redundant RFs for PFS. A risk score composed of these equally weighed RFs was significantly prognostic for PFS (HR = 1.67 for each additional RF; p<0.0001). Validation in an independent sample of 389 patients treated in different clinical settings with evaluation of response to salvage therapy by functional imaging instead of CT confirmed the excellent discrimination of risk groups and significant prognostication of PFS and overall survival (OS) after ASCT (HR = 1.70 and HR = 1.63, respectively; p<0.0001).
Conclusions : Based on this large study (n=1045), precise and valid risk prognostication in HL patients undergoing ASCT can be achieved with five easily available clinical RFs. The proposed prognostic score hence allows reliable stratification of patients for innovative therapeutic approaches in clinical practice and future trials.
Annals of Oncology , résumé, 2016