Prognosis of Progressive Follicular Lymphoma within 24 Months of First-Line Therapy Is Not Influenced By the Initial Regimen Intensity

Abstract

CONCLUSIONS Progression of follicular lymphoma (FL) within 24 months of initiating first-line therapy (POD24) is a strong driver of poor outcomes and is associated with a high risk of transformation. Previous reports suggest that POD24 has less prognostic significance in patients treated with rituximab alone as front-line therapy. We aimed to evaluate the impact of POD24 on outcome as well as the influence of the intensity of front-line therapy on the prognosis of POD24 in our local cohort of FL patients. We included patients with FL grade 1, 2 or 3A and stages II to IV who received front line therapy between 01/01/2014 and 31/12/2020 at our centre, and excluded patients treated with radiotherapy alone. Our primary objective was to describe and compare the clinical outcomes following different front-line regimens used in FL at our center. Rituximab (R) alone and R-Cyclophosphamide, Vincristine and Prednisone (R-CVP) were defined as attenuated-intensity regimens and R-CHOP (R-CVP with adriamycin) and bendamustine-rituximab (BR) as high-intensity regimens. The following endpoints were analyzed: event-free survival (EFS), defined as time from therapy initiation (D1C1) to progression, relapse, transformation to an aggressive lymphoma, or death of any cause, progression-free survival (PFS), defined as time from D1C1 to progression or death and overall survival (OS), defined as time from D1C1 to death of any cause. POD24 was defined as progression or relapse within 24 months of D1C1. We identified 85 patients with FL. At diagnosis, median age was 61 years (range: 38-85), 86 % had an ECOG performance score of 0-1, 81% had grade 1-2 FL, 91% had stage III-IV and 27% had high LDH. FLIPI score was available for 82 patients and 54% had a FLIPI of 3-5. Seventy-eight patients (92%) received a combination of rituximab and chemotherapy (R-chemo) and 7 (8%) received rituximab alone (R). Front line BR is approved at our center since November 2019. R-chemo regimens included R-CVP (40 patients, 47%), R-CHOP (29 patients, 34%) and BR (9 patients, 11%). Fifty-four patients received rituximab maintenance. Rituximab maintenance was not offered following BR. Twenty-eight (33%) patients had POD24 and 57 patients (67%) did not (non-POD24 group). Median follow-up was 5 years. Median and 5-year results for the 85 patients are: EFS 4.2 years and 45%, PFS 4.2 years and 45% and OS not reached and 86%. Patients with POD24 and non-POD24 had a 5-year OS of 66% (38-84) and 94% (81-98) (p=0.007) respectively. The proportion of POD24 among patients treated with R-chemo or R alone was 32% (25/78) and 43% (3/7). The rates of POD24 after R-CVP, R-CHOP and BR were 25% (10/40), 38% (11/29) and 44% (4/9), respectively. Among patients treated with R-chemo, 5-year OS was 67% for POD24 and 93% for non-POD24 (p=0.01). Among patients treated with an attenuated-intensity regimen, 5-year OS was 85% for POD24 and 93% for non-POD24 (p=0.567). Among patients with POD24, 5-year OS with an attenuated-intensity regimen was 85%, whereas it was 33% in the group of patients treated with R-CHOP or BR (p=0.18). Transformation incidence to an aggressive lymphoma was 15% at 5 years for the whole cohort, 32% in the POD24 group and 6% in the non-POD24 group (p=0.0004). BR was the regimen associated with the highest rate of transformation reaching a rate of 83% compared to none with R, 8% with R-CVP and 14% with R-CHOP (p=0.0005). Median time to transformation in aggressive lymphoma from D1C1 was 329 days (range 140-2688). On multivariable analysis, no patient- or disease-related factor before the first line treatment was associated with the occurrence of POD24. Our real-world study highlights the inferior outcome of patients with POD24 retrieved in pooled analysis from larger cohorts, irrespective of the intensity of the induction regimen. The small number of patients is a limitation of our study. The identification of clinical features associated with POD24 before 1L initiation is needed to improve outcomes of FL. Acknowledgments The study has been supported by the C3i Lymphoma Registry