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

Sarah Huet 1, 2 Edith Szafer-Glusman 3 Bruno Tesson 4 Luc Xerri 5, 6 Wayne J. Fairbrother 3 Kiran Mukhyala 3 Chris Bolen 3 Elizabeth Punnoose 3 Laurie Tonon 7 Catherine Chassagne-Clément 8 Pierre Feugier 9 Alain Viari 10, 11 Fabrice Jardin 12 Gilles Salles 8, 2 Pierre Sujobert 2, 1
1 UCBL - Université Claude Bernard Lyon 1
2 HCL - Hospices Civils de Lyon
3 Genentech, Inc.
4 Institut Carnot CALYM [Pierre-Benite]
5 Institut Paoli-Calmettes
6 AMU - Aix Marseille Université
7 Synergie Lyon Cancer [Lyon]
8 Centre Léon Bérard [Lyon]
9 Service d'Hématologie [CHRU Nancy]
10 ERABLE - Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale
Inria Grenoble - Rhône-Alpes
11 Baobab
PEGASE - Département PEGASE [LBBE]
12 GPL - Groupe d'étude des proliférations lymphoïdes
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.
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Sarah Huet, Edith Szafer-Glusman, Bruno Tesson, Luc Xerri, Wayne J. Fairbrother, et al.. BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab. American Journal of Hematology, Wiley, 2017, 92 (6), pp.515 - 519. ⟨10.1002/ajh.24701⟩. ⟨hal-01524901⟩

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