Autologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: An international, multicenter propensity matched study.

Abstract

8021 Background: Transformation of untreated indolent B-cell lymphoma (Tr-iNHL) is associated with poor outcomes. Current practices are extrapolated from prospective studies of de novo large B-cell lymphoma (DLBCL) or small retrospective studies. High dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) is used as consolidation in first remission (CR1) in some centers but the evidence-base is weak. Methods: CLL/SLL, MCL as primary diseases and non-DLBCL transformations were excluded. Propensity score analysis (PSM) using the “greedy match” algorithm was used to match the baseline covariates to adjust for potential selection bias. Landmark analysis was performed with time zero at 3 months after completion of front line chemotherapy (FLC). Kaplan-Meier method and the Cox proportional hazards model were was used for time-to-event analysis including progression-free survival (PFS) and overall survival (OS). Results: 319 transplant eligible patients (age <75, LVEF >45%, no severe lung disease, CR by PET or CT >3 months after FLC) who received >/= standard RCHOP intensity FLC were identified across three centers in Australia & US. 283 (89%) patients had follicular lymphoma, 30 (9%) marginal zone lymphoma, 6 (2%) other subtypes. 49 patients underwent HDC and ASCT in CR1, a matched cohort of 98 pts based on age, stage, HGBL-DH and ECOG PS at diagnosis was generated with a 1:2 ratio using PSM. After a median follow-up of 3.6 (min: 0.1, max: 18.3) years, ASCT was associated with significantly superior PFS on multivariable analysis (MVA) (HR 0.51, 0.27-0.98; P=0.043). Univariate analysis demonstrated a trend towards inferior OS in the ASCT cohort (HR 2.36; 0.87-6.42; P=0.092) with more deaths in the ASCT arm due to PD (8% v 4%). Of the 40 patients (41%) with relapsed disease in the non-ASCT cohort–15 patients underwent salvage HDC & ASCT with 7/15 (47%) ongoing CR; 10 patients underwent CAR-T therapy (5 relapse post ASCT, 4 refractory disease, 1 relapse post FLC) with 6/10 (60%) ongoing CR; 3 patients underwent allogeneic SCT (2 relapse post ASCT, 1 relapse post FLC) with 2/3 (67%) ongoing CR. Conclusions: Although ASCT in CR1 may improve initial duration of disease control in de novo Tr-iNHL, the impact on OS is less clear with effective salvage therapies in the CAR-T era.