R-CHOP Alone For Rituximab Naive Transformed Follicuar Lymphoma Has An Excellent Outcome
Authors: Chan Y L Tracey , Vydianath Bindu , Inman Charlotte F , Mahendra Prem , Malladi Ram , Chaganti Sridhar 
Published: October 2019

Abstract

Background
Treatment 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.

Methods
1900 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.

Results
The 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).

Conclusion
Our 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.