Wednesday, January 03, 2018 -- Purpose: Activation of the PI3K/mTOR signaling pathway is recurrent in different lymphoma types, and pharmacologic inhibition of the PI3K/mTOR pathway has shown activity in lymphoma patients. Here, we extensively characterized the in vitro and in vivo activity and the mechanism of action of PQR309 (bimiralisib), a novel oral selective dual PI3K/mTOR inhibitor under clinical evaluation, in preclinical lymphoma models. Experimental Design: This study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination, validation experiments on in vivo models and primary cells, proteomics and gene-expression profiling, and comparison with other signaling inhibitors. Results: PQR309 had in vitro antilymphoma activity as single agent and in combination with venetoclax, panobinostat, ibrutinib,
Tuesday, January 02, 2018 -- The response evaluation criteria in patients with Hodgkin lymphoma (HL) were designed for the assessment of chemotherapy and targeted molecular agents. We investigated the accuracy of 3-mo 18F-FDG PET/CT for the identification of HL patients responding to immune-checkpoint blockade by anti–programmed death 1 antibodies (anti-PD1). We also reported the frequency of new immune patterns of response and progression. Methods: Retrospectively, we recruited consecutive HL patients treated by anti-PD1 (pembrolizumab or nivolumab) at Gustave Roussy from 2013 to 2015. 18F-FDG PET/CT and contrast-enhanced CT scans were acquired every 3 mo. We recorded the best overall response according to the International Harmonization Project Cheson 2014 criteria and LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC) (2016 revised criteria). Patients achieving an objective
Thursday, January 04, 2018 -- Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1+ tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell
Thursday, January 04, 2018 -- The presence of bulky disease in Hodgkin lymphoma (HL), traditionally defined with a 1-dimensional measurement, can change a patient’s risk grouping and thus the treatment approach. We hypothesized that 3-dimensional measurements of disease burden obtained from baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), would more accurately risk-stratify patients. To test this hypothesis, we reviewed pretreatment PET-CT scans of patients with stage I-II HL treated at our institution between 2003 and 2013. Disease was delineated on prechemotherapy PET-CT scans by 2 methods: (1) manual contouring and (2) subthresholding of these contours to give the tumor volume with standardized uptake value ≥2.5. MTV and TLG were extracted from the
Tuesday, January 02, 2018 -- With improving supportive care, elderly patients may benefit from high-dose chemotherapy with autologous stem cell transplantation.
Thursday, January 04, 2018 -- Patients who indicated a decreased level of physical activity at 3 years after diagnosis had a worse overall and lymphoma-specific survival compared with those who did not report a change.