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RS mutation profile was tested on pre-treatment cell free DNA. Rate of unmeasurable MRD and impact of mutations and chronic lymphocytic leukemia-RS clonal relation on outcomes will be presented at the meeting. B Introduction: b Chemoimmunotherapy is the standard first line treatment of diffuse large B-cell lymphoma (DLBCL) variant of Richter syndrome (RS). [Extracted from the article]

Abstract Background In patients with non-valvular atrial fibrillation (NVAF) at high risk for stroke guidelines consistently recommend long-term oral anticoagulation (OAC) with a vitamin K antagonist. However recommendations remain ambiguous in respect to the precise OAC initiation regimens. Based on the clinical observation, that the initiation of OAC for NVAF varies considerably in daily practice, we aimed to assess the current practice in Switzerland. Methods Cross-sectional survey of randomly selected general practitioners, internists and cardiologists from different health care settings in an urban Swiss region that covers 1.4 million inhabitants. The main outcome measures were the preferred antithrombotic initiation regimen and long-term treatment in patients with newly diagnosed NVAF at high risk for stroke. Results We received 226 out of 388 (58.2%) surveys. Compared to physicians working in a hospital setting (33.6% of respondents) physicians in ambulatory care reported more years of experience and claimed lower-use (never or seldom) of guidelines in general (47.6 vs. 12.2%). Regarding long-term thromboembolic prophylaxis 93.7% of all responders followed current recommendation by choosing an OAC. When focussing on guideline-consistent correct OAC initiation (either low-dose initial OAC or a combination of LMWH and OAC) adherence dropped to 60.6% with hospital physicians demonstrating a significantly higher use of guideline-conform OAC regimens (79.7 vs. 51.0%). Medical speciality in non-hospital physicians was not related to correct guideline-use. Hospital setting remained independently associated with a guideline-conform OAC initiation regimen (OR 2.8, p = 0.023) when controlled for medical speciality, physicians' characteristics and clinical experience. Problems when starting an anticoagulation treatment were seldom reported (never or seldom accounting for 94.1% of all responses). Conclusions The guideline adherence with respect to OAC initiation regimens in NVAF was significantly lower when compared to long-term treatment and health care setting rather than medical speciality explained guideline-conform OAC initiation. The majority of the physicians did not consider the initiation of anticoagulation to be a major obstacle in outpatient care.

Background: The diffuse large B-cell lymphoma (DLBCL) variant of Richter transformation (DLBCL-RT) is typically chemoresistant with poor prognosis. Aiming to explore a chemotherapy-free treatment combination that triggers anti-tumour immune responses, we conducted a phase 2 study of atezolizumab (a PD-L1 inhibitor) in combination with venetoclax and obinutuzumab in patients with DLBCL-RT., Methods: This was a prospective, open-label, multicentre, single-arm, investigator-initiated, phase 2 study in 15 hospitals in Italy and Switzerland. Eligible patients had a confirmed diagnosis of chronic lymphocytic leukaemia or small lymphocytic lymphoma as per the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria with biopsy-proven transformation to DLBCL; had not previously received treatment for DLBCL-RT, although they could have received chronic lymphocytic leukaemia therapies; were aged 18 years or older; and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. No previous treatment with any of the drugs in the triplet combination was allowed. Patients received 35 cycles of 21 days of intravenous obinutuzumab (100 mg on day 1, 900 mg on day 2, 1000 mg on day 8 and day 15 of cycle 1; 1000 mg on day 1 of cycles 2-8) and intravenous atezolizumab (1200 mg on day 2 of cycle 1 and 1200 mg on day 1 of cycles 2-18), and continuous oral venetoclax (ramp-up from 20 mg/day on day 15 of cycle 1 according to chronic lymphocytic leukaemia schedule, then 400 mg/day from day 1 of cycle 3 to day 21 of cycle 35). The primary endpoint was overall response rate at day 21 of cycle 6 in the intention-to-treat population. We considered an overall response rate of 67% or more to be clinically active, rejecting the null hypothesis of a response of 40% or less. The study is registered with ClinicalTrials.gov, NCT04082897, and has been completed., Findings: Between Oct 9, 2019, and Oct 19, 2022, 28 patients were enrolled (12 [43%] male patients and 16 [57%] female patients). Median follow-up was 16·8 months (IQR 7·8-32·0). At cycle 6, 19 of 28 patients showed a response, yielding an overall response rate of 67·9% (95% CI 47·6-84·1). Treatment-emergent adverse events that were grade 3 or worse were reported in 17 (61%; 95% CI 40·6-78·5) of 28 patients, with neutropenia being the most frequent (11 [39%; 21·5-59·4] of 28 patients). Serious treatment-emergent adverse events were reported in eight (29%; 14·2-48·7) patients, which were most commonly infections (five [18%; 6·1-36·9] of 28 patients). There were two (7%) deaths attributable to adverse events during the study: one from sepsis and one from fungal pneumonia, which were not considered as directly treatment-related by the investigators. Six (21·4%) patients had immune-related adverse events, none of which led to discontinuation. No tumour lysis syndrome was observed., Interpretation: The atezolizumab, venetoclax, and obinutuzumab triplet combination was shown to be active and safe, suggesting that this chemotherapy-free regimen could become a new first-line treatment approach in patients with DLBCL-RT., Funding: Roche., Competing Interests: Declaration of interests AT reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen, Beigene, and Abbvie; support for attending meetings or travel from Abbvie, Janssen, and Beigene; and participation on a data safety monitoring board or advisory board from Janssen, Abbvie, Beigene, Lilly, and AstraZeneca. AMF reports consulting fees from Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen, Beigene, and AstraZeneca; support for attending meetings or travel from Abbvie, Janssen, Beigene, and AstraZeneca; and participation on a data safety monitoring board or advisory board from Janssen, Beigene, and AstraZeneca. ACo reports grants or contracts from Gilead, BMS, Beigene, Abbvie, Janssen-Cilag, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Abbvie, and Janssen-Cilag; support for attending meetings or travel from Janssen; and participation on a data safety monitoring board or advisory board from BMS. MC reports grants or contracts from Johnson & Johnson and Abbvie; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbvie and AstraZeneca; support for attending meetings or travel from Johnson & Johnson, Abbvie, and AstraZeneca; and participation on a data safety monitoring board or advisory board from Johnson & Johnson, Abbvie, AstraZeneca, Beigene, and GSK. RC reports support for the present manuscript from the US National Institutes of Health and National Cancer Institute (R01CA196703–01). PLZ reports consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda, BMS, MSD, Roche, Gilead, Novartis, Abbvie, Beigene, Kyowa Kirin, and Janssen. MMot reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events; support for attending meetings or travel; and participation on a data safety monitoring board or advisory board from Abbvie, Janssen, and AstraZeneca. GG reports grants from Associazione Italiana per la Ricerca sul Cancro and Piano Nazionale di Ripresa e Resilienza; consulting fees from Abbvie, AstraZeneca, Beiene, Hikma, and Johnson & Johnson; and participation on a data safety monitoring board or advisory board from Abbvie, AstraZeneca, Beigene, Hikma, Johnson & Johnson, and Lilly. LS reports consulting from Abbvie, Beigene, Lilly, AstraZeneca, Janssen, and Merck; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbvie, Beigene, Lilly, Octapharma, AstraZeneca, Janssen, and Merck; support for attending meetings or travel from AstraZeneca, Janssen, and Beigene; and participation on a data safety monitoring board or advisory board from Merck. RCa reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbvie, Gilead, Gentilipharma, Pierre Fabre, Celgene, and Menarini stemline; support for attending meetings or travel from Pierre Fabre, Beigene, and Servier; and participation on a data safety monitoring board or advisory board from Celgene, Abbvie, Gentilipharma, and Daichi Samkio. TZ report consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, Novartis, Gilead, Janssen, AstraZeneca, Lilly, and Abbvie. EZ reports consulting fees from Abbvie, Beigene, BMS, Cures, Elly and Lilly, Incyte, Ipsen, Merck, Miltenyibiomedicine, and Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbvie, AstraZeneca, Beigene, and Gilead; support for attending meetings or travel from Abbvie; and participation on a data safety monitoring board or advisory board from Merck. DR reports support for the present manuscript from Adaptive; grants or contracts, consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbvie, AstraZeneca, Beigene, BMS, Janssen, and Lilly. All other authors declare no competing interests. No honoraria or payments were made for authorship., (Copyright © Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To understand the knowledge and awareness of palliative care in the Italian-speaking Swiss general population, describing main misconceptions or false beliefs and their relationship with attitudes towards palliative care., Methods: Cross-sectional representative population survey (N = 313)., Results: We observed a high awareness of «palliative care,» although it is mainly associated with pain management and the very last days of life. While false beliefs are relatively rare, there is low awareness of goals, targets, and services offered by palliative care. Overall the Italian-speaking Swiss population has a good predisposition towards palliative care, but negative attitudes are more common among those who lack knowledge. More than one-third of respondents are interested in receiving more information about palliative care, especially from their healthcare providers or through dedicated information points., Conclusion and Practice Implications: Health communication interventions to promote palliative care are needed because there is still significant unclarity about the goals of palliative care, which negatively affects its acceptance. This study instructs on how to intervene specifically in the Italian-speaking part of Switzerland, including what to communicate and how. Further, our findings can inspire similar studies in other Swiss regions or countries that can optimize recognition, knowledge, and understanding and contribute to filling gaps in populations' health service demand and utilization., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Diviani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chronic lymphocytic leukemia (CLL) has a heterogeneous biological behavior, which is highly influenced by its immunogenetic, epigenetic, and genomic properties. The remarkably variable clinical course of the disease has been associated with genetic features such as chromosomal abnormalities, the presence of either high or low numbers of somatic hypermutations (SHM) in the variable region of the immunoglobulin heavy chain locus ( IGHV ), and somatic mutations of several specific driver genes. Next-generation sequencing (NGS) technologies have provided a comprehensive characterization of the genomic and epigenomic landscape in CLL, elucidating important underlying mechanisms of the disease's biology. The scope of this review is to summarize the most recent discoveries about novel genetic and epigenetic alterations, discussing their impact on clinical outcomes and response to currently available therapy.

Objectives: Oncology palliative care (PC) services seek to improve quality of life in patients with cancer. PC providers face significant systemic obstacles, stemming from insufficient collaboration between healthcare providers. This study explores these obstacles and strategies to help facilitate successful collaboration amongst healthcare providers at a systemic level., Methods: A multicenter qualitative study was conducted via interviews and focus groups. Fifty employees in Italian-speaking Switzerland were interviewed, along with ten relatives of oncology patients. Framework analysis was used to identify and categorize the most prominent themes., Results: Three main themes were identified: knowledge of and connection to other healthcare approaches; beliefs, attitudes and behavior regarding collaboration; and values, attitudes and beliefs towards life, end-of-life and optimal care approaches for oncology patients., Conclusions: Strategies that promote interprofessional collaboration and oncology PC services should foster a cultural shift towards perceiving these services as a medical specialty, thereby contributing to quality patient care., Implications: An overview of potential limitations is provided, in addition to a timeline of interprofessional collaboration which would help to optimize oncology PC services., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Influenza vaccination efficacy is reduced after hematopoietic stem cell transplantation (HSCT) and patient factors determining vaccination outcomes are still poorly understood., Methods: We investigated the antibody response to seasonal influenza vaccination in 135 HSCT patients and 69 healthy volunteers (HVs) in a prospective observational multicenter cohort study. We identified patient factors associated with hemagglutination inhibition titers against A/California/2009/H1N1, A/Texas/2012/H3N2, and B/Massachusetts/2012 by multivariable regression on the observed titer levels and on seroconversion/seroprotection categories for comparison., Results: Both regression approaches yielded consistent results but regression on titers estimated associations with higher precision. HSCT patients required 2 vaccine doses to achieve average responses comparable to a single dose in HVs. Prevaccination titers were positively associated with time after transplantation, confirming that HSCT patients can elicit potent antibody responses. However, an unrelated donor, absolute lymphocyte counts below the normal range, and treatment with calcineurin inhibitors lowered the odds of responding., Conclusions: HSCT patients show a highly heterogeneous vaccine response but, overall, patients benefited from the booster shot and can acquire seroprotective antibodies over the years after transplantation. Several common patient factors lower the odds of responding, urging identification of additional preventive strategies in the poorly responding groups., Clinical Trials Registration: NCT03467074., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and in genetically modified mouse models, and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-κB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments., (© 2022 by The American Society of Hematology.)

As life expectancy has increased, a growing number of people experience conditions, including cancers, that carry complex health and social needs. Palliative care services have the potential to address these needs but face significant obstacles. One major obstacle is suboptimal interprofessional collaboration. This study's goal was an in-depth exploration of interactional and organizational barriers and supports of collaboration in palliative care in Switzerland. We sought the perspectives of health care professionals, patients' family members and leaders and experts in oncology/palliative care delivery (key informants) through interviews and focus groups with fifty HPs and key informants and ten patients' family members. Qualitative analyses of interviews and focus groups used framework analysis. We identified three major themes of interaction: personal characteristics, communication, and connectedness with other health care professionals; and three major organizational themes: service characteristics, standardized communication and processes, and service coordination and promotion. Based on our findings, we recommend that health care professionals consider strategies to increase their collaboration and communication skills and opportunities to interact. We advocate the implementation of methods for coordinating services, standardization of consultation/referral procedures and communication between health care professionals, and the promotion of underutilized services to foster successful, sustainable collaboration., Competing Interests: The authors have declared that no competing interests exist.

This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Bone marrow biopsies at diagnosis and before the 2nd induction cycle were obtained to assess the therapeutic impact on leukemic blasts and microenvironment. Increased bone marrow angiogenesis, as assessed by microvessel density (MVD), was found at AML diagnosis and differed significantly between the WHO categories. Morphological analysis revealed a higher initial MVD in AML with myelodysplasia-related changes (AML-MRC) and a more substantial decrease of microvascularization after lenalidomide exposure. A slight increase of T-bet-positive TH1-equivalents was identifiable under lenalidomide. In the subgroup of patients with AML-MRC, the progression-free survival differed between the two treatment regimens, showing a potential but not significant benefit of lenalidomide. We found no correlation between the cereblon genotype (the target of lenalidomide) and treatment response or prognosis. In conclusion, addition of lenalidomide may be beneficial to elderly patients suffering from AML-MRC, where it leads to a reduction of microvascularization and, probably, to an intensified specific T cell-driven anti-leukemic response.