Chronic Lymphocytic Leukemia
June 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:Targeting the tumor promoting effects of adenosine in chronic lymphocytic leukemia.
Authors:Cai Y, Feng L, Wang X
Institution:Department of Hematology, Provincial Hospital Affiliated to Shandong University, No. 324, Jingwu Road, Jinan, Shandong 250021, People's Republic of China. No. 324, Jingwu Road, Jinan, Shandong 250021, People's Republic of China. Electronic address: No. 324, Jingwu Road, Jinan, Shandong 250021, People's Republic of China; Shandong University School of Medicine, Jinan, Shandong 250012, People's Republic of China. Electronic address:
Journal:Crit Rev Oncol Hematol. 2018 Jun;126:24-31. doi: 10.1016/j.critrevonc.2018.03.022. Epub 2018 Mar 29.

2:Comparable Efficacy of Idelalisib Plus Rituximab and Ibrutinib in Relapsed/refractory Chronic Lymphocytic Leukemia: A Retrospective Case Matched Study of the Polish Adult Leukemia Group (PALG).
Authors:Pula B, Budziszewska BK, Rybka J, Gil L, Subocz E, Dlugosz-Danecka M, Zawirska D, Waszczuk-Gajda A, Iskierka-Jazdzewska E, Kopacz A, Szymczyk A, Czyz J, Lech-Maranda E, Warzocha K, Jamroziak K
Institution:Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland Warsaw, Poland. Wroclaw Medical University, Wroclaw, Poland. University of Medical Sciences, Poznan, Poland. Warsaw, Warsaw, Poland. Hospital, Lodz, Poland. of Lublin, Lublin, Poland. Warsaw, Poland. Education, Warsaw, Poland. Warsaw, Poland. Warsaw, Poland.
Journal:Anticancer Res. 2018 May;38(5):3025-3030. doi: 10.21873/anticanres.12557.

3: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.

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:Lenalidomide maintenance therapy in previously treated chronic lymphocytic leukaemia (CONTINUUM): a randomised, double-blind, placebo-controlled, phase 3 trial.
Authors:Chanan-Khan AA, Zaritskey A, Egyed M, Vokurka S, Semochkin S, Schuh A, Kassis J, Simpson D, Zhang J, Purse B, Foa R
Institution:Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL, USA. Electronic address: Petersburg, Russia. Republic. University, Moscow, Russia. Umberto 1, Sapienza University, Rome, Italy.
Journal:Lancet Haematol. 2017 Nov;4(11):e534-e543. doi: 10.1016/S2352-3026(17)30168-0. Epub 2017 Sep 25.

10:Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia.
Authors:Brumbaugh Paradis H, Alter D, Llerandi D
Institution:Duke University Medical Center.
Journal:Clin J Oncol Nurs. 2017 Oct 1;21(5):604-610. doi: 10.1188/17.CJON.604-610.

11: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.

12:Lenalidomide maintenance after first-line therapy for high-risk chronic lymphocytic leukaemia (CLLM1): final results from a randomised, double-blind, phase 3 study.
Authors:Fink AM, Bahlo J, Robrecht S, Al-Sawaf O, Aldaoud A, Hebart H, Jentsch-Ullrich K, Dorfel S, Fischer K, Wendtner CM, Nosslinger T, Ghia P, Bosch F, Kater AP, Dohner H, Kneba M, Kreuzer KA, Tausch E, Stilgenbauer S, Ritgen M, Bottcher S, Eichhorst B, Hallek M
Institution:Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University Hospital of Cologne, Cologne, Germany. Electronic address:; Gemeinschaftspraxis fur Hamatologie und Onkologie, Leipzig, Germany.; Zentrum fur Innere Medizin, Hamatologie/Onkologie, Stauferklinikum Schwabisch-Gmund, Germany.; Internistische Gemeinschaftspraxis, Magdeburg, Germany.; Onkologische Gemeinschaftspraxis, Dresden, Germany.
Journal:Lancet Haematol. 2017 Oct;4(10):e475-e486. doi: 10.1016/S2352-3026(17)30171-0. Epub 2017 Sep 12.

13:Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies.
Authors:Kurtz SE, Eide CA, Kaempf A, Khanna V, Savage SL, Rofelty A, English I, Ho H, Pandya R, Bolosky WJ, Poon H, Deininger MW, Collins R, Swords RT, Watts J, Pollyea DA, Medeiros BC, Traer E, Tognon CE, Mori M, Druker BJ, Tyner JW
Institution:Division of Hematology & Medical Oncology, Oregon Health & Science University, Portland, OR 97239.; Howard Hughes Medical Institute, Oregon Health & Science University, Portland, OR 97239.; Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239.; Microsoft Research, Redmond, WA 98052.; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112.
Journal:Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):E7554-E7563. doi: 10.1073/pnas.1703094114. Epub 2017 Aug 7.

14:Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment.
Authors:Hallek M
Institution:Department I of Internal Medicine, Center for Integrated Oncology Koln Bonn, Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases," University of Cologne, Kerpener Strasse 62, Koln, 50937, Germany.
Journal:Am J Hematol. 2017 Sep;92(9):946-965. doi: 10.1002/ajh.24826.

15: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.

16: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.

17:Targeting B Cell Signaling in Chronic Lymphocytic Leukemia.
Authors:Arnason JE, Brown JR
Institution:Beth Israel Deaconess Medical Center, Harvard Medical School, BIDMC, 330 Brookline Ave, Boston, MA, 02215, USA. MA, 02215, USA.
Journal:Curr Oncol Rep. 2017 Sep;19(9):61. doi: 10.1007/s11912-017-0620-7.

18:Impact of novel agents on patient-relevant outcomes in patients with previously untreated chronic lymphocytic leukemia who are not eligible for fludarabine-based therapy.
Authors:Singh M, Mealing S, Baculea S, Cote S, Whelan J
Institution:a ICON Health Economics , London , UK.
Journal:J Med Econ. 2017 Oct;20(10):1066-1073. doi: 10.1080/13696998.2017.1357563. Epub 2017 Aug 9.

19:Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor-Modified T Cells After Failure of Ibrutinib.
Authors:Turtle CJ, Hay KA, Hanafi LA, Li D, Cherian S, Chen X, Wood B, Lozanski A, Byrd JC, Heimfeld S, Riddell SR, Maloney DG
Institution:Cameron J. Turtle, Kevin A. Hay, Laila-Aicha Hanafi, Shelly Heimfeld, Stanley R. Riddell, and David G. Maloney, Fred Hutchinson Cancer Research Center; Cameron J. Turtle, Sindhu Cherian, Xueyan Chen, Brent Wood, Stanley R. Riddell, and David G. Maloney, University of Washington; Daniel Li, Juno Therapeutics, Seattle, WA; and Arletta Lozanski and John C. Byrd, The Ohio State University, Columbus, OH.
Journal:J Clin Oncol. 2017 Sep 10;35(26):3010-3020. doi: 10.1200/JCO.2017.72.8519. Epub 2017 Jul 17.

20:Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT.
Authors:van Gelder M, Ziagkos D, de Wreede L, van Biezen A, Dreger P, Gramatzki M, Stelljes M, Andersen NS, Schaap N, Vitek A, Beelen D, Lindstrom V, Finke J, Passweg J, Eder M, Machaczka M, Delgado J, Kruger W, Raida L, Socie G, Jindra P, Afanasyev B, Wagner E, Chalandon Y, Henseler A, Schoenland S, Kroger N, Schetelig J
Institution:Department of Internal Medicine, University Medical Center Maastricht, Maastricht, the Netherlands. Electronic address:; Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.; Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands; DKMS Clinical Trials Unit, Dresden, Germany.; Department of Medicine V, University of Heidelberg, Heidelberg, Germany.; Division of Stem Cell Transplantation and Immunotherapy, University Hospital Schleswig-Holstein, Kiel, Germany.
Journal:Clin Lymphoma Myeloma Leuk. 2017 Oct;17(10):667-675.e2. doi: 10.1016/j.clml.2017.06.007. Epub 2017 Jun 17.

21:A Phase II Trial Evaluating the Safety of Rapid Infusion of Ofatumumab in Patients with Previously Treated Chronic Lymphocytic Leukemia.
Authors:Donnellan W, Berdeja JG, Shipley D, Arrowsmith ER, Wright D, Lunin S, Brown R, Essell JH, Flinn IW
Institution:Sarah Cannon Research Institute, Nashville, Tennessee, USA.
Journal:Oncologist. 2017 Oct;22(10):1156-e111. doi: 10.1634/theoncologist.2017-0236. Epub 2017 Jul 7.

22:Risk of cutaneous T-cell lymphoma in patients with chronic lymphocytic leukemia and other subtypes of non-Hodgkin lymphoma.
Authors:Chang TW, Weaver AL, Shanafelt TD, Habermann TM, Wriston CC, Cerhan JR, Call TG, Brewer JD
Institution:Department of Dermatology, Mayo Clinic, Rochester, MN, USA. USA.
Journal:Int J Dermatol. 2017 Nov;56(11):1125-1129. doi: 10.1111/ijd.13653. Epub 2017 Jul 7.

23:The safety of Bruton's tyrosine kinase inhibitors for the treatment of chronic lymphocytic leukemia.
Authors:Tran PN, O'Brien S
Institution:a Division of Hematology-Oncology , University of California Irvine , Orange , CA , USA. , USA.
Journal:Expert Opin Drug Saf. 2017 Sep;16(9):1079-1088. doi: 10.1080/14740338.2017.1344213. Epub 2017 Jun 23.

24: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.

25: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.

26:Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes.
Authors:Xochelli A, Baliakas P, Kavakiotis I, Agathangelidis A, Sutton LA, Minga E, Ntoufa S, Tausch E, Yan XJ, Shanafelt T, Plevova K, Boudjogra M, Rossi D, Davis Z, Navarro A, Sandberg Y, Vojdeman FJ, Scarfo L, Stavroyianni N, Sudarikov A, Veronese S, Tzenou T, Karan-Djurasevic T, Catherwood M, Kienle D, Chatzouli M, Facco M, Bahlo J, Pott C, Pedersen LB, Mansouri L, Smedby KE, Chu CC, Giudicelli V, Lefranc MP, Panagiotidis P, Juliusson G, Anagnostopoulos A, Vlahavas I, Antic D, Trentin L, Montillo M, Niemann C, Dohner H, Langerak AW, Pospisilova S, Hallek M, Campo E, Chiorazzi N, Maglaveras N, Oscier D, Gaidano G, Jelinek DF, Stilgenbauer S, Chouvarda I, Darzentas N, Belessi C, Davi F, Hadzidimitriou A, Rosenquist R, Ghia P, Stamatopoulos K
Institution:Institute of Applied Biosciences, CERTH, Thessaloniki, Greece.; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.; Department of informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece.; Division of Experimental Oncology and Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Journal:Clin Cancer Res. 2017 Sep 1;23(17):5292-5301. doi: 10.1158/1078-0432.CCR-16-3100. Epub 2017 May 23.

27:Treatment of chronic lymphocytic leukemia in older adults.
Authors:Rowswell-Turner RB, Barr PM
Institution:James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: NY, USA.
Journal:J Geriatr Oncol. 2017 Sep;8(5):315-319. doi: 10.1016/j.jgo.2017.04.004. Epub 2017 May 6.

28:Chronic lymphocytic leukaemia genomics and the precision medicine era.
Authors:Ghamlouch H, Nguyen-Khac F, Bernard OA
Institution:Institut National De La Sante Et De La Recherche Medicale (INSERM) U1170, Villejuif, France. Biologique, Hopital Pitie-Salpetriere, APHP, Paris, France. Villejuif, France.
Journal:Br J Haematol. 2017 Sep;178(6):852-870. doi: 10.1111/bjh.14719. Epub 2017 Apr 25.

29: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.

30: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.

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