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The BCL2 inhibitor venetoclax is transforming the management of patients with chronic lymphocytic leukemia (CLL), given its high efficacy in relapsed/refractory CLL as observed in both early-phase and randomized clinical trials. The present study aimed to determine whether venetoclax is effective and well tolerated in patients with CLL or Richter's syndrome (RS) in a real-world setting and to highlight factors impacting survival. Data from a venetoclax French compassionate use program were collected for 67 patients (60 with CLL and 7 with RS). Most patients presented adverse genetic features, such as TP53 disruption (74%) or complex karyotype (58%). Tumor lysis syndrome was observed in 14 (22%) patients, and 16 (24%) patients were hospitalized for grade III/IV infection. In the CLL cohort, ORR was 75 %, 1-year PFS was 61% (95% CI = 47–72%) and 1-year OS 70% (95% CI = 56–80%). No impact of TP53 disruption was noted while complex karyotype was identified as a predictor of both inferior PFS (HR = 3.46; 95% CI = 1–12; log-rank p = 0.03) and OS (HR = 3.2; 95% CI = 0.9–11.4, log-rank p = 0.047). Among the seven patients with RS, two achieved an objective response to venetoclax; however, the median OS was only 1.1 month. The well-balanced safety/efficacy profile of venetoclax is confirmed in this real-world setting. Complex karyotype should be evaluated as a predictive factor of survival for patients treated by venetoclax. [ABSTRACT FROM AUTHOR]

Preclinical and clinical studies have suggested that cancer treatment with antitumor antibodies induces a specific adaptive T cell response. A central role in this process has been attributed to CD4+ T cells, but the relevant T cell epitopes, mostly derived from non-mutated self-antigens, are largely unknown. In this study, we have characterized human CD20-derived epitopes restricted by HLA-DR1, HLA-DR3, HLA-DR4, and HLA-DR7, and investigated whether T cell responses directed against CD20-derived peptides can be elicited in human HLA-DR-transgenic mice and human samples. Based on in vitro binding assays to recombinant human MHC II molecules and on in vivo immunization assays in H-2 KO/HLA-A2+-DR1+ transgenic mice, we have identified 21 MHC II-restricted long peptides derived from intracellular, membrane, or extracellular domains of the human non-mutated CD20 protein that trigger in vitro IFN-γ production by PBMCs and splenocytes from healthy individuals and by PBMCs from follicular lymphoma patients. These CD20-derived MHC II-restricted peptides could serve as a therapeutic tool for improving and/or monitoring anti-CD20 T cell activity in patients treated with rituximab or other anti-CD20 antibodies. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity. [ABSTRACT FROM AUTHOR]

T cell non-Hodgkin lymphomas (T-NHLs) are aggressive malignancies which have a high risk of life-threatening complications. However, their prognosis in the intensive care unit (ICU) setting has not yet been assessed. We conducted a study including 87 ICU patients either with newly diagnosed T-NHLs or those undergoing first-line therapy admitted between January 1, 2000, and December 31, 2014. The primary subtypes were peripheral T cell lymphoma (PTCL) (n = 41, 47%), anaplastic large-cell lymphoma (ALCL) (n = 13, 15%), and adult T-leukaemia/lymphoma (ATLL) (n = 11, 13%). Six in every ten patients had malignancy-related complications (haemophagocytic syndrome 37%, tumour lysis syndrome 18% and hypercalcaemia 9%), while infections accounted for one quarter of ICU admissions. Nine fungal infections were documented, including six invasive aspergillosis. Urgent chemotherapy was started in the ICU in 59% of the patients, and urgent surgery was required in 13%. ICU and day-90 mortality were 22% and 41%, respectively. Multivariate analysis showed that SOFA score at day 1, age, sepsis and haemophagocytic syndrome were independent predictors of day-90 mortality. Compared to 66 ICU-matched controls with non-Hodgkin B cell lymphomas, patients with T-NHLs had a similar ICU survival. Overall survival rates of patients with T cell NHLs and B cell NHLs were 20% and 46%, respectively (hazard ratio for death associated with T cell NHLs 2.00 [1.12-3.58]). Patients with T cell NHLs had a very poor long-term outcome. Although the high rate of short-term survival suggests that an ICU trial is a reasonable option for patients newly diagnosed for the malignancy, extended stay in the ICU or further readmission should be considered only for highly selected patients who respond to the haematological treatment. [ABSTRACT FROM AUTHOR]