BCL2 as a marker to identify refractory and at risk of relapse disease in classic Hodgkin Lymphoma patients. Its blokeadge as a potential directed-tehrapy.

OTERO, VICTORIA; CUGLIARI, SILVANA; GARCÍA RIVELLO, HERNÁN; RANUNCOLO, STELLA MARIS; SCHUTZ, NATALIA; ZERGA, MARTA; JAUK, FEDERICO; GAMBOA-CEDEÑO, ANGÉLICA; FANTL, DOROTEA; ROJAS-BILBAO, ERICA; NUÑEZ, MYRIAM

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE), XXI Reunión Anual de la Sociedad Argentina de Biología (SAB), XXXI Reunión Anual de la Sociedad A; 2019

Sociedad Argentina de iNvetsigación Clínica (SAIC).

Refractory and relapsed disease (RRD) is currently the challenge when treating classic Hodgkin Lymphoma (cHL) patients. There is no specific therapy rather than rescue chemotherapy which fails in 50% of the cases and associates with high toxicity. We have previously reported that the alternative NFkB pathway, mediated by Rel-B and NIK, plays a key role in cHL survival through high BCL2 expression levels. We aimed to analyze if mediators of this pathway and BCL2 could be useful as prognosis markers and would represent targetable factors in RRD.We analyzed NIK and BCL2 expression in Hodgkin Reed-Sternberg cells in the lymph node biopsies of 113 cHL naïve of therapy patients by IHQ [52 female Md age (range) 36 (6-88), 61 male 40.7 (9-78)]. The univariate analysis showed no correlation between NIK or BCL2 expression and the clinical and pathological parameters, including the PET Scan indicated at the end of the first line treatment. The statistical significance was maintained in multivariate analysis (Cox Regression p=0.01). NIK expression did not associate with prognosis but the BCL2 expression level correlated with lack of response to conventional therapy and both early and late disease progression. The survival analysis, using the Kaplan-Meir curves, showed that patients with ≥60% positive HRS cells had a shorter disease-free survival (DFS) [Log Rank Test p=0.002] and a reduced overall survival (OS) [Log Rank Test p=0.02].Human cHL cell lines that express BCL2 protein, were sensitive to venetoclax, a specific BCL2 inhibitor. The drug induced a citostatic effect with cell arrest in S-Phase.We found that the alternative NFkB pathway plays an important role in the refractory and relapsed Hodgkin disease, being BCL2 a key downstream target. BCL2 performed well as a prognosis marker identifying refractory patients and those that relapsed. We believe BCL2 directed-therapy should be explored in cHL patients that express this protein in the biopsy performed at diagnosis.