BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab.

Huet S1,2, Szafer-Glusman E3, Tesson B4, Xerri L5, Fairbrother WJ3, Mukhyala K3, Bolen C3, Punnoose E3, Tonon L6, Chassagne-Clément C7, Feugier P8, Viari A6,9, Jardin F10, Salles G2,11, Sujobert P1,2.

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Abstract

BCL2 mutations have been suggested to confer an adverse prognosis to follicular lymphoma (FL) patients, but their prognostic value has not been assessed in patients treated with a rituximab-containing regimen. Here we evaluated the prognostic value of BCL2 mutations in a large prospective cohort of 252 patients with FL treated with immunochemotherapy in the PRIMA randomized trial. Using a DNA-targeted sequencing approach, we detected amino acid altering mutations in 135 patients (54%) and showed that these mutations were probably mediated by the over-activation of AICDA (activation-induced cytidine deaminase) in the context of the t(14;18) translocation. The BCL2 variants identified in PRIMA patients affected the BH1, BH2, and BH3 functional motifs at a lower frequency than the N-terminus and flexible loop domain, with mostly conservative aminoacid changes. With a median follow-up of 6.7 years, we did not observe any impact of BCL2 mutations either on overall survival or progression-free survival.