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      Management of adverse events associated with idelalisib treatment in chronic lymphocytic leukemia and follicular lymphoma: A multidisciplinary position paper

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          Abstract

          The introduction of new therapeutic agents in chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), including the new kinase inhibitor idelalisib, has changed the therapeutic landscape of these diseases. However, the use of idelalisib is associated with a peculiar profile of side effects, which require an optimization of the current approach to prophylaxis and supportive treatment. Moving from the recognition that the abovementioned issue represents an unmet need in CLL and FL, a multidisciplinary panel of experts was convened to produce a consensus document aiming to provide practical recommendations for the management of the side effects during idelalisib therapy for CLL and FL. The present publication represents a consensus document from a series of meetings held during 2017. The Panel generated clinical key questions using the criterion of clinical relevance through a Delphi process and explored 4 domains, ie, diarrhea/colitis, transaminitis, pneumonitis, and infectious complications. Using the consensus method, the Panel was able to shape recommendations which may assist hematologist to minimize adverse events and guarantee adherence to treatment in patients with CLL and FL candidate to receive idelalisib.

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          Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

          Noninvasive ventilation (NIV) with a face mask is relatively ineffective at preventing endotracheal intubation in patients with acute respiratory distress syndrome (ARDS). Delivery of NIV with a helmet may be a superior strategy for these patients.
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            Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia.

            In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of the lipid kinase PI3Kδ, was evaluated in 54 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) with adverse characteristics including bulky lymphadenopathy (80%), extensive prior therapy (median 5 [range 2-14] prior regimens), treatment-refractory disease (70%), unmutated IGHV (91%), and del17p and/or TP53 mutations (24%). Patients were treated at 6 dose levels of oral idelalisib (range 50-350 mg once or twice daily) and remained on continuous therapy while deriving clinical benefit. Idelalisib-mediated inhibition of PI3Kδ led to abrogation of Akt phosphorylation in patient CLL cells and significantly reduced serum levels of CLL-related chemokines. The most commonly observed grade ≥3 adverse events were pneumonia (20%), neutropenic fever (11%), and diarrhea (6%). Idelalisib treatment resulted in nodal responses in 81% of patients. The overall response rate was 72%, with 39% of patients meeting the criteria for partial response per IWCLL 2008 and 33% meeting the recently updated criteria of PR with treatment-induced lymphocytosis.(1,2) The median progression-free survival for all patients was 15.8 months. This study demonstrates the clinical utility of inhibiting the PI3Kδ pathway with idelalisib. Our findings support the further development of idelalisib in patients with CLL. These trials were registered at clinicaltrials.gov as #NCT00710528 and #NCT01090414.
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              Incidence of pneumonitis with use of PD-1 and PD-L1 inhibitors in non-small cell lung cancer: A Systematic Review and Meta-analysis of trials.

              PD-1/PD-L1 inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis, and differences according to type of inhibitors and prior chemotherapy use.
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                Author and article information

                Contributors
                cut@unife.it
                Journal
                Hematol Oncol
                Hematol Oncol
                10.1002/(ISSN)1099-1069
                HON
                Hematological Oncology
                John Wiley and Sons Inc. (Hoboken )
                0278-0232
                1099-1069
                05 September 2018
                February 2019
                : 37
                : 1 ( doiID: 10.1002/hon.v37.1 )
                : 3-14
                Affiliations
                [ 1 ] Hematology Section, Department of Medical Sciences, Azienda Ospedaliero‐Universitaria, Arcispedale S. Anna University of Ferrara Ferrara Italy
                [ 2 ] IRCCS Policlinico S. Matteo Foundation Pavia Italy
                [ 3 ] Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine University of Pisa Pisa Italy
                [ 4 ] Gastroenterology and Transplant Hepatology “Papa Giovanni XXIII” Hospital Bergamo Italy
                [ 5 ] Università Vita‐Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele Milan Italy
                [ 6 ] Division of Gastroenterology, San Giovanni Battista Hospital University of Torino Turin Italy
                [ 7 ] Department of Hematology Niguarda Cancer Center Niguarda Hospital Milano Milan Italy
                [ 8 ] Department of Diseases of the Thorax Ospedale GB Morgagni Forlì Italy
                [ 9 ] Department of Respiratory Diseases & Allergy Aarhus University Hospital Aarhus Denmark
                [ 10 ] Infectious Disease Unit, Teaching Hospital S. Orsola‐Malpighi Alma Mater Studiorum ‐ University of Bologna Bologna Italy
                [ 11 ] Institute of Hematology Lorenzo e Ariosto Seràgnoli University of Bologna Bologna Italy
                Author notes
                [*] [* ] Correspondence

                Antonio Cuneo, Hematology Section, Department of Medical Sciences, Azienda Ospedaliero‐Universitaria, Arcispedale S. Anna, University of Ferrara, Via Aldo Moro, 8, 44124, Cona, Ferrara, Italy.

                Email: cut@ 123456unife.it

                Author information
                http://orcid.org/0000-0003-2001-1308
                http://orcid.org/0000-0002-4414-8934
                http://orcid.org/0000-0002-2112-2651
                Article
                HON2540 HON-18-0154.R1
                10.1002/hon.2540
                6585802
                30187496
                603948ce-8cb4-4485-91d4-830562713516
                © 2018 The Authors Hematological Oncology Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 26 June 2018
                : 09 July 2018
                : 10 July 2018
                Page count
                Figures: 7, Tables: 6, Pages: 12, Words: 4196
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                hon2540
                February 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.4 mode:remove_FC converted:20.06.2019

                adverse events,chronic lymphocytic leukemia,follicular lymphoma,idelalisib

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