Inhibidores de BTK de segunda generación: zanubrutinib Nuevo agente terapéutico para desórdenes linfoproliferativos B

Bruton's tyrosine kinase is a tyrosine kinase expressed in the entire hematopoietic lineage, except for T cell progenitors, and plays an essential role in the BCR pathway. Inhibition of BTK has proven to be an effective strategy in some lymphomas and chronic lymphocytic leukemia. Ibrutinib and acalabrutinib are BTK inhibitors approved in Argentina.Zanubrutinib is a more specific iBTK, which would explain some differences with those previously developed. Many studies with zanubrutinib in different B-lymphoproliferative syndromes are in development or with different follow-up and it demonstrate a more selective inhibition with more complete and sustained occupation of BTK, which would result in greater benefits in efficacy and safety.La tirosina kinasa de Bruton es una tirosina kinasa expresada en todo el linaje hematopoyético, excepto en los progenitores de células T, y cumple un papel esencial en la vía del BCR. La inhibición de la BTK ha probado ser una estrategia efectiva en algunos linfomas y en leucemia linfática crónica. Ibrutinib y acalabrutinib son inhibidores de BTK aprobados en Argentina. Zanubrutinib es un iBTK más específico, lo que explicaría algunas diferencias con los previamente desarrollados. Muchos estudios con zanubrutinib en diferentes síndromes linfoproliferativos B se encuentran en desarrollo o con diferente tiempo de seguimiento y demuestran una inhibición más selectiva por parte de zanubrutinib con ocupación más completa y sostenida de la BTK, lo que resultaría en mayores beneficios en eficacia y seguridad. ia y seguridad

Apoptotic regulator BCL-2 blockade aS a potential therapy in classical Hodgkin Lymphoma

The challenge in classical Hodgkin Lymphoma (cHL) management is the 30–40% of refractory/relapsed cases. Aims: The aim of this work was to determine whether NIK and BCL-2 could be useful as prognosis biomarkers in cHL. In addition, we evaluated BCL-2 as a directed-therapy in cHL cell lines using venetoclax. Main methods: We evaluated NIK and BCL-2 expression in 112 untreated cHL patients' lymph-node biopsies by immunohistochemistry. cHL cell lines were treated with venetoclax alone or combined with vincristine or doxorubicin. Cell viability, metabolic activity and cell death were analyzed by trypan-blue exclusion method, MTS assay and FDA/IP staining respectively. Key findings: No correlation between NIK or BCL-2 expression and the majority of the clinical parameters was found. Patients with ≥60% BCL-2+ HRS-cells had a shorter disease-free survival (DFS) and overall survival (OS) (p = 0.002, p = 0.02 respectively). A decision tree analysis, in a 30 patients subgroup, showed that patients with <60% NIK+ HRS-cells but with ≥60% BCL-2+ HRS-cells had a worse outcome in terms of DFS and OS. These parameters performed better as prognosis indicators as compared to the diagnosis bone marrow status. Human cHL cell lines U-H01, KM-H2, L1236, SUPHD1, L540 showed sensitivity to venetoclax. The co-treatment effect of venetoclax and vincristine or doxorubicin on cell viability was diverse depending on the cell line evaluated. Significance: BCL-2 should be considered as a prognosis biomarker as well as a potential new therapeutic target in cHL. We report for the first time the cytotoxic effect of venetoclax in human cHL cell lines.Fil: Gamboa Cedeño, Angélica María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; ArgentinaFil: Díaz, Mariángeles. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Cristaldo, Nancy. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Otero, Victoria. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Schutz, Natalia. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Fantl, Dorotea. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Cugliari, María Silvana. Universidad de Buenos Aires; ArgentinaFil: Zerga, Marta Elisa. Universidad de Buenos Aires; ArgentinaFil: Rojas Bilbao, Érica. Universidad de Buenos Aires; ArgentinaFil: Jauk, Federico. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Garcia Rivello, Hernan Jorge. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Núñez, Myriam Carmen. Universidad de Buenos Aires; ArgentinaFil: Ranuncolo, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional e Ingeniería Biomédica - Hospital Italiano. Instituto de Medicina Traslacional e Ingeniería Biomédica.- Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional e Ingeniería Biomédica; Argentin

Retrospective Multicenter Real-Life Study on the First-Line Treatment of Classical Hodgkin Lymphoma in Argentina

Abstract There are no data in Argentina on the response rates to first-line treatment of classical Hodgkin Lymphoma (cHL) outside clinical trials. A total of 498 patients from 7 public and private hospitals in Argentina were retrospectively examined. The median follow-up was 37.4 months (CI 95% 17.7–63.5). The median time from diagnosis to treatment was 22 days (IQR 14–42), which was significantly longer in public hospitals (49.3 (IC 95% 38.5–60.2) versus 32.5 (IC 95% 27–38); p = 0.0027). A total of 96.8% of patients were treated with ABVD.:84.3% achieved complete remission (CR) and 6.02% partial remission (PR), being the CR rate higher in private hospitals. End-of-treatment metabolic CR was achieved in 85.4% (n = 373). The interim PET scan was widely used in our cohort (70.5%; n = 351), but in only 23.3% (n = 116) was the treatment strategy response-adapted. The 5-year progression-free survival (PFS) was 76% (CI 95% 70–81). The 2 and 5-years-OS rates were 91% (CI 95% 88–94%) and 85% (CI 95% 80–89%), respectively. No differences in OS were found between public and private institutions (p = 0.27). This is one of the largest retrospective cHL cohorts reported. In Argentina ABVD is the chemotherapy regimen of choice and, although it is well tolerated, it is not exempt from toxicity. We showed that early initiation of treatment impacts the induction results. Although the use of PET scan is widespread, only a minority of patients was treated with respons- adapted strategies. The use of PET-guided treatment is strongly encouraged