Chronic Lymphocytic Leukemia
April 2018 Issue

Nearly every major medical breakthrough over the past 50 years can be attributed to new discoveries that were made possible through meticulous biomedical research. Many diseases and conditions that previously took a heavy toll on patients in terms of both morbidity and mortality are now either treatable or preventable thanks in large part to painstaking research that expanded the frontiers of scientific knowledge and moved the most promising basic research developments into tangible health benefits through human clinical trails. Ongoing research is also the key that will open the door to additional major medical advances and breakthroughs in the future.

Our staff at Medifocus is committed to keeping our subscribers to the Medifocus Digest Alert on Chronic Lymphocytic Leukemia abreast of the latest new research developments that have recently been published in the medical literature for this condition. In this issue of the Digest Alert, you will find a focused list of hand-picked journal article references that represent the latest advances in basic and clinical research for Chronic Lymphocytic Leukemia. These articles represent the current state-of-the-art of the research that will hopefully lead to additional major advances and breakthroughs in the clinical management of Chronic Lymphocytic Leukemia. You can access the summaries of each article referenced below by simply clicking on the article Title.

We will continue to update you with the latest scientific and clinical developments through the Medifocus Digest Alert on Chronic Lymphocytic Leukemia every 3 months. Thank you for your ongoing subscription to this publication.

Elliot Jacob, Ph.D.
Vice-President - Content, Inc.

1:Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.
Authors:Seymour JF, Kipps TJ, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Gerecitano J, Robak T, De la Serna J, Jaeger U, Cartron G, Montillo M, Humerickhouse R, Punnoose EA, Li Y, Boyer M, Humphrey K, Mobasher M, Kater AP
Institution:From the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne, Melbourne, VIC (J.F.S.), and the John Curtin School of Medical Research, Australian National University, Canberra, ACT (J.D.) - all in Australia; the University of California School of Medicine, San Diego (T.J.K.), and Genentech, South San Francisco (E.A.P., Y.L., M. Mobasher) - both in California; University Hospital Cologne and the Center for Integrated Oncology Cologne-Bonn, Cologne, Germany (B.E.); St. James's University Hospital, Leeds (P.H.), and F. Hoffmann-La Roche, Welwyn Garden City (M.B., K.H.) - both in the United Kingdom; Segal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal (S.A.), and the Departments of Medicine and Oncology, University of Calgary, Calgary, AB (C.O.) - all in Canada; Memorial Sloan Kettering Cancer Center, New York (J.G.); the Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland (T.R.); Hospital Universitario 12 de Octubre, Madrid (J.D.S.); Medical University of Vienna, Department of Medicine I, Division of Hematology and Hemostaseology, Vienna (U.J.); the Department of Hematology, Centre Hospitalier Universitaire Montpellier, Montpellier, France (G.C.); the Department of Onco-Hematology, Division of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milan (M. Montillo); AbbVie, North Chicago, IL (R.H.); and the Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam (A.P.K.).
Journal:N Engl J Med. 2018 Mar 22;378(12):1107-1120. doi: 10.1056/NEJMoa1713976.

2:Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.
Authors:Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA
Institution:From the Departments of Pediatrics (S.L.M., S.A.G.) and Pathology and Laboratory Medicine (C.H.J., B.L.L.), Perelman School of Medicine, and Abramson Cancer Center (C.H.J., B.L.L.), University of Pennsylvania, and the Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherapy Program, Children's Hospital of Philadelphia (S.L.M., S.A.G.) - all in Philadelphia; the Department of Pediatrics and Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, and the Pauline Allen Gill Center for Cancer and Blood Disorders, Children's Health, Dallas (T.W.L.); the Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo (J.B.); the Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Deu Barcelona, Barcelona (S.R.); the Department of Pediatrics and Internal Medicine, University of Utah, Salt Lake City (M.B.); the Department of Pediatrics, Faculty of Medicine, University of Montreal, and the Hematology Oncology Division and Charles-Bruneau Cancer Center, Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal (H.B.), and the Division of Haematology/Oncology/Bone Marrow Transplantation, Hospital for Sick Children, Toronto (J.K.) - all in Canada; the Division of Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, University Hospital Frankfurt, Frankfurt, Germany (P.B.); the Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis (M.R.V., H.E.S.); Children's Mercy Hospital and Clinics, Kansas City, MO (G.D.M.); Aflac Cancer and Blood Disorders Center, Emory University, Atlanta (M.Q.); the Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, and the Cancer Research Institute Ghent (CRIG), Ghent, Belgium (B.D.M.); the Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto, Japan (H.H.); the Department of Pediatrics, Stanford University School of Medicine, Stanford (K. Schlis, K.L.D.), and the Division of Hematology, Oncology, Blood and Marrow Transplant, Children's Hospital Los Angeles, USC Keck School of Medicine, Los Angeles (M.A.P.) - all in California; the Division of Pediatric Blood and Marrow Transplant, Duke University Medical Center, Durham, NC (P.L.M.); Oregon Health and Science University, Portland (E.R.N.); C.S. Mott Children's Hospital, Ann Arbor, MI (G.A.Y.); the Stem Cell Transplantation Unit, St. Anna Children's Hospital, Vienna (C.P.); University Hospital Robert Debre and University Paris Diderot (A. Baruchel), and Saint-Louis Hospital and University Paris Diderot (N.B.), Paris; the Royal Children's Hospital, Melbourne, VIC, Australia (F.M.); Clinica Pediatrica Universita degli Studi di Milano Bicocca, Monza, Italy (A. Balduzzi); and Novartis Pharmaceuticals (P.W., T.T., M.L., Y.Z., K. Sen, D.L.) and Novartis Institutes for Biomedical Research (K.T.M.) - both in East Hanover, NJ.
Journal:N Engl J Med. 2018 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866.

3:A single-institution retrospective cohort study of first-line R-EPOCH chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic leukaemia karyotype as an adverse prognostic factor.
Authors:Rogers KA, Huang Y, Ruppert AS, Salem G, Stephens DM, Heerema NA, Andritsos LA, Awan FT, Byrd JC, Flynn JM, Maddocks KJ, Jones JA
Institution:Division of Hematology, The Ohio State University, Columbus, OH, USA.
Journal:Br J Haematol. 2018 Jan;180(2):259-266. doi: 10.1111/bjh.15035. Epub 2017 Nov 28.

4:Bruton's tyrosine kinase inhibitors: first and second generation agents for patients with Chronic Lymphocytic Leukemia (CLL).
Authors:Thompson PA, Burger JA
Institution:a Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA. Houston , TX , USA.
Journal:Expert Opin Investig Drugs. 2018 Jan;27(1):31-42. doi: 10.1080/13543784.2018.1404027. Epub 2017 Nov 15.

5:Approach to Richter transformation of chronic lymphocytic leukemia in the era of novel therapies.
Authors:Khan M, Siddiqi R, Thompson PA
Institution:Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd, Houston, TX, 77030-4009, USA. Holcombe Blvd, Houston, TX, 77030-4009, USA.
Journal:Ann Hematol. 2018 Jan;97(1):1-15. doi: 10.1007/s00277-017-3149-9. Epub 2017 Oct 23.

6:Therapeutics targeting Bcl-2 in hematological malignancies.
Authors:Ruefli-Brasse A, Reed JC
Institution:Roche, Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel 4070, Switzerland Hoffmann-La Roche Ltd, Grenzacherstrasse 124, Basel 4070, Switzerland.
Journal:Biochem J. 2017 Oct 23;474(21):3643-3657. doi: 10.1042/BCJ20170080.

7:FCR achieves long-term durable remissions in patients with IGHV-mutated CLL.
Authors:Chai-Adisaksopha C, Brown JR
Institution:Department of Medicine and. Hamilton, ON, Canada; and. Harvard Medical School, Boston, MA.
Journal:Blood. 2017 Nov 23;130(21):2278-2282. doi: 10.1182/blood-2017-07-731588. Epub 2017 Oct 12.

8:Venetoclax for the treatment of chronic lymphocytic leukemia.
Authors:Gentile M, Petrungaro A, Uccello G, Vigna E, Recchia AG, Caruso N, Bossio S, De Stefano L, Palummo A, Storino F, Martino M, Morabito F
Institution:a Hematology Unit, Department of Hemato-Oncology , Ospedale Annunziata , Cosenza , Italy. , Italy. , Italy. , Italy. Aprigliano , Italy. Aprigliano , Italy. Aprigliano , Italy. Aprigliano , Italy. Aprigliano , Italy. Aprigliano , Italy.
Journal:Expert Opin Investig Drugs. 2017 Nov;26(11):1307-1316. doi: 10.1080/13543784.2017.1386173. Epub 2017 Oct 9.

9:Novel synthetic drugs currently in clinical development for chronic lymphocytic leukemia.
Authors:Robak P, Robak T
Institution:a Department of Experimental Hematology , Medical University of Lodz , Lodz , Poland.
Journal:Expert Opin Investig Drugs. 2017 Nov;26(11):1249-1265. doi: 10.1080/13543784.2017.1384814. Epub 2017 Oct 3.

10:Combination therapy with the type II anti-CD20 antibody obinutuzumab.
Authors:Klein C, Bacac M, Umana P, Fingerle-Rowson G
Institution:a Roche Pharmaceutical Research & Early Development , Roche Innovation Center Zurich , Zurich , Switzerland. Zurich , Zurich , Switzerland. Zurich , Zurich , Switzerland. Switzerland.
Journal:Expert Opin Investig Drugs. 2017 Oct;26(10):1145-1162. doi: 10.1080/13543784.2017.1373087.

11:Diagnosis of CLL revisited: increased specificity by a modified five-marker scoring system including CD200.
Authors:Kohnke T, Wittmann VK, Bucklein VL, Lichtenegger F, Pasalic Z, Hiddemann W, Spiekermann K, Subklewe M
Institution:Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. Germany. Germany. Germany. Germany.
Journal:Br J Haematol. 2017 Nov;179(3):480-487. doi: 10.1111/bjh.14901. Epub 2017 Aug 18.

12:New drug discovery approaches targeting recurrent mutations in chronic lymphocytic leukemia.
Authors:Tripathi R, Lee-Verges E, Higashi M, Gimenez N, Rosich L, Lopez-Guerra M, Colomer D
Institution:a Experimental Therapeutics in Lymphoid Malignancies Group, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hematopathology Unit , Hospital Clinic, CIBERONC , Barcelona , Spain.
Journal:Expert Opin Drug Discov. 2017 Oct;12(10):1041-1052. doi: 10.1080/17460441.2017.1362387. Epub 2017 Aug 4.

13:Ibrutinib versus previous standard of care: an adjusted comparison in patients with relapsed/refractory chronic lymphocytic leukaemia.
Authors:Hansson L, Asklid A, Diels J, Eketorp-Sylvan S, Repits J, Soltoft F, Jager U, Osterborg A
Institution:Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Journal:Ann Hematol. 2017 Oct;96(10):1681-1691. doi: 10.1007/s00277-017-3061-3. Epub 2017 Jul 31.

14:IGHV mutational status testing in chronic lymphocytic leukemia.
Authors:Crombie J, Davids MS
Institution:Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Massachusetts.
Journal:Am J Hematol. 2017 Dec;92(12):1393-1397. doi: 10.1002/ajh.24808. Epub 2017 Jul 29.

15:Safety and efficacy of Ofatumumab in chronic lymphocytic leukemia: a systematic review and meta-analysis.
Authors:Wu Y, Wang Y, Gu Y, Xia J, Kong X, Qian Q, Hong Y
Institution:a Medical Institution Conducting Clinical Trials for Human Used Drug, The Fifth People's Hospital of Shanghai , Fudan University , Shanghai , China.; b Department of General Psychiatry, Shanghai Mental Health Center , Shanghai Jiaotong University , Shanghai , China.; c Department of Hematology, The Fifth People's Hospital of Shanghai , Fudan University , Shanghai , China.; d Department of Osteology, The Fifth People's Hospital of Shanghai , Fudan University , Shanghai , China.
Journal:Hematology. 2017 Dec;22(10):578-584. doi: 10.1080/10245332.2017.1333974. Epub 2017 Jun 3.

16:Targeting antigen-independent proliferation in chronic lymphocytic leukemia through differential kinase inhibition.
Authors:Slinger E, Thijssen R, Kater AP, Eldering E
Institution:Cancer Center Amsterdam, Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands. Amsterdam, The Netherlands. Center, Amsterdam, The Netherlands. Amsterdam, The Netherlands. Amsterdam, The Netherlands. Center, Amsterdam, The Netherlands.
Journal:Leukemia. 2017 Dec;31(12):2601-2607. doi: 10.1038/leu.2017.129. Epub 2017 May 2.

17:Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL.
Authors:Howard DR, Munir T, McParland L, Rawstron AC, Milligan D, Schuh A, Hockaday A, Allsup DJ, Marshall S, Duncombe AS, O'Dwyer JL, Smith AF, Longo R, Varghese A, Hillmen P
Institution:Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK. University of Leeds, Leeds, UK. Leeds, UK. Birmingham, UK. Oxford University Hospital Trust, Oxford, UK. University of Leeds, Leeds, UK. Kingdom and Hull York Medical School, University of Hull, Hull, UK. of Leeds, Leeds, UK. of Leeds, Leeds, UK. of Leeds, Leeds, UK. (LICAP), University of Leeds, Leeds, UK.
Journal:Leukemia. 2017 Nov;31(11):2416-2425. doi: 10.1038/leu.2017.96. Epub 2017 Mar 24.

18:Efficacy and safety of biosimilar epoetin alpha in patients with chronic lymphoid neoplasms and chemotherapy-induced anaemia: An observational, retrospective, monocentric analysis.
Authors:Broccoli A, Argnani L, Stefoni V, Gandolfi L, Zinzani PL
Institution:Institute of Hematology "L. e A. Seragnoli", University of Bologna, Bologna, Italy. Italy. Italy. Italy. Italy.
Journal:Hematol Oncol. 2018 Feb;36(1):136-143. doi: 10.1002/hon.2412. Epub 2017 Mar 23.

19:Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL.
Authors:Munir T, Howard DR, McParland L, Pocock C, Rawstron AC, Hockaday A, Varghese A, Hamblin M, Bloor A, Pettitt A, Fegan C, Blundell J, Gribben JG, Phillips D, Hillmen P
Institution:Department of Haematology, St James's University Hospital, Leeds, UK. University of Leeds, Leeds, UK. University of Leeds, Leeds, UK. Leeds, UK. University of Leeds, Leeds, UK. Liverpool, UK.
Journal:Leukemia. 2017 Oct;31(10):2085-2093. doi: 10.1038/leu.2017.65. Epub 2017 Apr 20.

20:Severe pneumonia associated with ibrutinib monotherapy for CLL and lymphoma.
Authors:Kreiniz N, Bejar J, Polliack A, Tadmor T
Institution:Hematology Unit, Bnai Zion Medical Center, Haifa, Israel. School, Jerusalem, Israel.
Journal:Hematol Oncol. 2018 Feb;36(1):349-354. doi: 10.1002/hon.2387. Epub 2017 Feb 3.

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