Abstract

Background:Although most patients with follicular lymphoma (FL) follow an indolent course with long‐lasting remissions, surviving more than 20 years after diagnosis, a small proportion of patients (20‐25%) has worse outcome due to early relapse or transformation to an aggressive form of lymphoma. The current risk prognosticators are based on the Follicular Lymphoma International Prognostic Index (FLIPI). There is not a perfect marker to predict those at higher risk of disease progression. FL with short remission duration has been established as a poor prognostic marker for survival and the optimal therapy for these patients is really not known.Aims:To analyze the clinicopathological features of refractory and early relapsed FL, the role of aggressive regimens and correlation between the treatment modality and outcome.Methods:In total, 9 patients with the primary refractory and early relapsed FL were diagnosed in Institute for radiology and oncology of Serbia during the period 2014‐2016. The treatment modality, the response, and follow‐up were registered for all the patients.Results:The median age of patients was 64 years (range, 48‐69). There were 5 male and 4 female patients. All patients were diagnosed with FL (grades 1‐3). There were 3 patients within each histologic grade. All patients presented with Ann Arbor stage III or IV disease and high FLIPI score. The bulky disease was present in 8 patients. Only three patients had normal serum LDH. All patients were treated with immunochemotherapy, R‐CVP or R‐CHOP. The median follow‐up was 33 months (range, 6‐57). Primary refractory disease was registered in 3 patients that had bulky disease, splenomegaly, and elevated serum LDH, who received non‐anthracycline, based regimen and progressed during induction therapy. One patient with primary refractory lymphoma died during induction therapy. Six patients were treated with an anthracycline‐based regimen. The overall response rate (ORR) for all R‐CHOP treated patients was 100% (50% PR and 50% CR after induction therapy). Relapse was documented during Rituximab maintenance within the first 8 months after the induction therapy in non‐refractory patients. Eight patients received Fludarabine‐based second‐line regimen with ORR of 89%. One patient died due to Richter's transformation during Fludarabine treatment. One patient who was transplant‐eligible experienced severe infectious complications following high dose therapy but later responded on local radiotherapy (RT) combined with low dose corticosteroid therapy. The second relapse was registered in three patients. They were treated with involved field RT with good response. Seven patients were still alive at the time of the last follow‐up and all of them remained in achieved response.Summary/Conclusion:The major needs are to upfront identify FL patients, for whom existing immunochemotherapeutic strategies are suboptimal and to find the best second‐line options for these patients. ASCT should be introduced within ≤1 year of treatment failure, early in the course of disease in order to preserve bone marrow capacity. Patients that are not candidates for ASCT can benefit from a less aggressive approach like RT, so there is a potential role of immunomodulators and PI3K inhibitors in overcoming the chemoresistance and establishing durable disease control.

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