R-CHOP Alone For Rituximab Naive Transformed Follicuar Lymphoma Has An Excellent Outcome

Abstract

▪ BackgroundTreatment of transformed follicular lymphoma (TFL) remains undefined and there is no consensus on the role of consolidation after induction chemotherapy. Outcomes for TFL in the pre-rituximab era were poor with a reported median overall survival (OS) of only 1.7 years1. This study investigates whether R-CHOP is an effective therapy for patients with TFL and which patient factors present at transformation help to predict outcome. Methods1900 lymphoma diagnoses from January 2000 - June 2012 were retrospectively screened and identified 60 patients with transformed indolent lymphoma. 40 eligible patients with histologically confirmed TFL were identified for this study. Overall survival (OS) and progression-free survival (PFS) were the primary study end-points. ResultsThe median follow up time for the cohort was 66 months (interquartile range (IQR) - 25-92 months) and the median age at diagnosis of TFL was 60 years (52-68 years). The majority (60%) of the cohort had high-grade (HG) transformation subsequent to diagnosis of follicular lymphoma (asynchronous TFL) with a median time to transformation of 48 months (24-78 mo). 32.5% of patients were simultaneously diagnosed with follicular lymphoma (FL) and HG disease (synchronous TFL). In a minority (3%), FL was diagnosed after HG disease.Univariate analysis revealed no significant relationship between outcome and patient age, sex or disease stage. However, patients with an elevated LDH (defined as >1.5x the upper limit of normal) at the time of diagnosis had a significantly reduced OS (5 mo vs 86 mo; p=0.003) and PFS (2.25 mo vs 56 mo; p=0.02). When compared with synchronous TFL, patients with asynchronous TFL had a reduced median survival (9 mo vs 67 mo; p=0.03) and PFS (7 mo vs 67 mo; p=0.003).When multivariate analysis is performed, elevated LDH and asynchronous TFL remain significant factors in determining PFS (p=0.021 and p=0.008 respectively). However, only elevated LDH remains a significant factor in determining OS (p=0.002).25/40 patients were treated with R-CHOP for TFL, with the remaining 15 either treated palliatively: steroids and etoposide (n=8), radiotherapy (n=1); with CHOP (n=4) or another R-chemo (n=2; R-ESCHAP; R-CVP). All R-CHOP treated patients were rituximab naïve. Of the 25 patients treated with R-CHOP: 20 were treated with R-CHOP alone, 2 received R-CHOP and another chemotherapy, 1 had R-CHOP and autograft and 2 received R-CHOP and allograft.In our cohort, R-CHOP treated patients had a 5-year OS of 62%, a median OS of 86 months (31-120 months) and PFS of 56 months (14-86 months). This represents a marked improvement in outcome compared to historic data, which showed a 5-year OS of 33% for TFL patients treated with CHOP alone2. The patients treated with R-CHOP alone (without further chemotherapy, autograft or allograft) had a similar outcome with a median OS of 86 months (37-120 months) and median PFS of 56 months (11-86 months). ConclusionOur results demonstrate the excellent outcomes achieved with R-CHOP alone in rituximab naïve patients with transformed follicular lymphoma. Patients with TFL presenting with synchronous disease and non-elevated LDH have significantly improved outcomes. In such patients, we may consider reserving consolidation with autograft or allograft for the future.1. Al-Tourah, A. J. et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology26,5165–9 (2008).2. Al-Tourah, A. J. et al. Addition of Rituximab to CHOP Chemotherapy Significantly Improves Survival of Patients with Transformed Lymphoma. Blood (ASH Annual Meeting Abstracts)110, (2007). Disclosures:Chaganti:Roche: Membership on an entity's Board of Directors or advisory committees, Receipt of travel grant Other.Transformed follicular lymphomaNumber of patients40Male:Female ratio47.5 : 52.5Age at TFL diagnosis (median)60Median follow up in months (95% confidence interval)66 (43-89)Timing of TFL diagnosisNo (%)FL diagnosed before (asynchronous)24 (60%)Synchronous diagnosis13 (32.5%)FL diagnosed after HG NHL3 (7.5%)Time to transformation for asynchronous TFL – months (95% confidence interval)48 (22-74)HG stage (%)1-214 (23.3%)3-445 (75%)unknown1 (1.7%)LDH<1.5x ULN22 (55.5%)>1.5x ULN14 (35%)unknown4 (10%)