BCL2 blockade in refractory and relapsed classic Hodgkin Lymphoma. Venetoclax sensitizes cells to first line treatment

GAMBOA-CEDEÑO ANGÉLICA; MARIANGELES DÍAZ; CRISTALDO, NANCY; OTERO, VICTORIA; SCHUTZ, NATALIA; FANTL, DOROTEA; CUGLIARI. SILVANA; ZERGA, MARTA; ROJAS-BILBAO, ERICA; JAUK VITALI, FEDERICO; GARCIA-RIVELLO HERNÁN; NUÑEZ, MYRIAM; RANUNCOLO STELLA MARIS

San Diego, California

Conferencia; 2020 American Association for Cancer Research (AACR) Annual Meeting; 2020

American Association for Cancer Research (AACR)

Nowadays the challenge when treating classic Hodgkin Lymphoma (cHL) is the 30-40% of refractory and relapsed cases. Our results suggest that BCL2 could play a role in the refractory and relapsed cHL. We have previously reported that the constitutive alternative NFkB signaling, due to NIK stabilization, plays a role in cHL survival by sustained high BCL2 levels. We aimed to analyze whether NIK and BCL2 could be useful as prognosis markers and would represent potential targetable factors.We evaluated NIK and BCL2 expression in Hodgkin Reed-Sternberg (HRS) cells in 112 cHL lymph node biopsies. No correlation between NIK or BCL2 expression and the clinical parameters was found in univariate or multivariate analysis. The Kaplan-Meir curves, showed that patients with ≥60% BCL2 positive HRS cells had a reduced disease-free survival and overall survival [Log Rank Test p=0.002, p=0.02 respectively]. Human cHL cell lines showed S-Phase/G2-M arrest or cell death when treated with venetoclax, a selective BCL2 inhibitor. Furthermore, venetoclax monotherapy, sensitized cHL cells to vincristine and doxorubicin. BCL2 expression correlated with lack of response to conventional therapy and both early and late disease progression. We believe patients that express BCL2 in the diagnosis lymph node biopsy could benefit from its inhibition.