Chronic Lymphocytic Leukemia
August 2017 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: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.

2:Obinutuzumab: what is there to learn from clinical trials?
Authors:Cartron G, Watier H
Institution:Departement d'Hematologie Clinique, Centre Hospitalier Universitaire (CHU), Montpellier, France. (CNRS), Universite de Montpellier, Montpellier, France.
Journal:Blood. 2017 Aug 3;130(5):581-589. doi: 10.1182/blood-2017-03-771832. Epub 2017 Jun 5.

3:Akt inhibitor MK-2206 in combination with bendamustine and rituximab in relapsed or refractory chronic lymphocytic leukemia: Results from the N1087 alliance study.
Authors:Larsen JT, Shanafelt TD, Leis JF, LaPlant B, Call T, Pettinger A, Hanson C, Erlichman C, Habermann TM, Reeder C, Nikcevich D, Bowen D, Conte M, Boysen J, Secreto C, Lesnick C, Tschumper R, Jelinek D, Kay NE, Ding W
Institution:Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Journal:Am J Hematol. 2017 Aug;92(8):759-763. doi: 10.1002/ajh.24762. Epub 2017 Jun 1.

4:BCL-2 as a therapeutic target in chronic lymphocytic leukemia.
Authors:Daniel C, Mato AR
Institution:Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. Pennsylvania, Philadelphia, Pennsylvania.
Journal:Clin Adv Hematol Oncol. 2017 Mar;15(3):210-218.

5:Advances in the treatment of relapsed/refractory chronic lymphocytic leukemia.
Authors:Shustik C, Bence-Bruckler I, Delage R, Owen CJ, Toze CL, Coutre S
Institution:McGill University Health Centre, Montreal, Quebec, Canada. Canada. Calgary, AB, Canada. BC Cancer Agency and The University of British Columbia, Vancouver, BC, Canada. USA.
Journal:Ann Hematol. 2017 Jul;96(7):1185-1196. doi: 10.1007/s00277-017-2982-1. Epub 2017 Apr 7.

6:Duvelisib: a phosphoinositide-3 kinase delta/gamma inhibitor for chronic lymphocytic leukemia.
Authors:Vangapandu HV, Jain N, Gandhi V
Institution:a Department of Experimental Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA. Houston , TX , USA. Cancer Center , Houston , TX , USA.
Journal:Expert Opin Investig Drugs. 2017 May;26(5):625-632. doi: 10.1080/13543784.2017.1312338. Epub 2017 Apr 13.

7:Lenalidomide in the treatment of chronic lymphocytic leukemia.
Authors:Itchaki G, Brown JR
Institution:a Department of Medical Oncology , Dana Farber Cancer Institute , Boston , MA , USA. USA.
Journal:Expert Opin Investig Drugs. 2017 May;26(5):633-650. doi: 10.1080/13543784.2017.1313230. Epub 2017 Apr 17.

8:Targeted therapy in the treatment of chronic lymphocytic leukemia: facts, shortcomings and hopes for the future.
Authors:Molica S
Institution:a Department of Hematology-Oncology , Azienda Ospedaliera Pugliese-Ciaccio , Catanzaro , Italy.
Journal:Expert Rev Hematol. 2017 May;10(5):425-432. doi: 10.1080/17474086.2017.1313108. Epub 2017 Apr 12.

9:Ibrutinib in CLL: a focus on adverse events, resistance, and novel approaches beyond ibrutinib.
Authors:Kaur V, Swami A
Institution:Department of Medicine, Division of Hematology/Oncology, University of Virginia, Charlottesville, VA, USA.
Journal:Ann Hematol. 2017 Jul;96(7):1175-1184. doi: 10.1007/s00277-017-2973-2. Epub 2017 Mar 24.

10:Factors predicting survival in chronic lymphocytic leukemia patients developing Richter syndrome transformation into Hodgkin lymphoma.
Authors:Mauro FR, Galieni P, Tedeschi A, Laurenti L, Del Poeta G, Reda G, Motta M, Gozzetti A, Murru R, Caputo MD, Campanelli M, Frustaci AM, Innocenti I, Raponi S, Guarini A, Morabito F, Foa R, Gentile M
Institution:Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Policlinico Umberto I, Rome. Mazzoni, Ascoli Piceno. Roma Tor Vergata, Rome. Policlinico, Milan. University, Policlinico Umberto I, Rome. University, Policlinico Umberto I, Rome. University, Policlinico Umberto I, Rome. University, Policlinico Umberto I, Rome. University, Policlinico Umberto I, Rome.
Journal:Am J Hematol. 2017 Jun;92(6):529-535. doi: 10.1002/ajh.24714. Epub 2017 Apr 18.

11:What Is Optimal Front-Line Therapy for Chronic Lymphocytic Leukemia in 2017?
Authors:Voorhies BN, Stephens DM
Institution:Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84112, USA. Medicine, University of Utah, Salt Lake City, UT, 84112, USA. Salt Lake City, UT, 84112, USA.
Journal:Curr Treat Options Oncol. 2017 Feb;18(2):12. doi: 10.1007/s11864-017-0450-8.

12:Magic pills: new oral drugs to treat chronic lymphocytic leukemia.
Authors:Vitale C, Griggio V, Todaro M, Salvetti C, Boccadoro M, Coscia M
Institution:a Division of Hematology , University of Torino, AOU Citta della Salute e della Scienza di Torino , Torino , Italy.; b Department of Molecular Biotechnology and Health Sciences , University of Torino , Torino , Italy.
Journal:Expert Opin Pharmacother. 2017 Mar;18(4):411-425. doi: 10.1080/14656566.2017.1293655. Epub 2017 Feb 22.

13:A phase 1/2 trial of ublituximab, a novel anti-CD20 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma or chronic lymphocytic leukaemia previously exposed to rituximab.
Authors:Sawas A, Farber CM, Schreeder MT, Khalil MY, Mahadevan D, Deng C, Amengual JE, Nikolinakos PG, Kolesar JM, Kuhn JG, Sportelli P, Miskin HP, O'Connor OA
Institution:Center for Lymphoid Malignancies, Columbia University Medical Center, New York, NY, USA. NY, USA. NY, USA. NY, USA.
Journal:Br J Haematol. 2017 Apr;177(2):243-253. doi: 10.1111/bjh.14534. Epub 2017 Feb 21.

14:A multicenter, single-arm, Phase II clinical trial of bendamustine monotherapy in patients with chronic lymphocytic leukemia in Japan.
Authors:Ogawa Y, Izutsu K, Kiguchi T, Choi I, Takatsuka Y, Ando K, Suzumiya J
Institution:Department of Hematology and Oncology, Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. of Public School Teachers, Fukuyama, Japan. Fukuoka, Japan. Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. Japan.
Journal:Int J Hematol. 2017 May;105(5):631-637. doi: 10.1007/s12185-016-2178-9. Epub 2017 Feb 3.

15:Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial.
Authors:Zelenetz AD, Barrientos JC, Brown JR, Coiffier B, Delgado J, Egyed M, Ghia P, Illes A, Jurczak W, Marlton P, Montillo M, Morschhauser F, Pristupa AS, Robak T, Sharman JP, Simpson D, Smolej L, Tausch E, Adewoye AH, Dreiling LK, Kim Y, Stilgenbauer S, Hillmen P
Institution:Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. Electronic address: School, Boston, MA, USA. Ospedale San Raffaele and Universita Vita-Salute San Raffaele, Milan, Italy. School of Medicine, Brisbane, Australia. Italy. France. Hospital, Lodz, Poland. Eugene, OR, USA. University in Prague, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.
Journal:Lancet Oncol. 2017 Mar;18(3):297-311. doi: 10.1016/S1470-2045(16)30671-4. Epub 2017 Jan 28.

16:Ibrutinib: A Review in Chronic Lymphocytic Leukaemia.
Authors:Deeks ED
Institution:Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Journal:Drugs. 2017 Feb;77(2):225-236. doi: 10.1007/s40265-017-0695-3.

17:Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study.
Authors:Seymour JF, Ma S, Brander DM, Choi MY, Barrientos J, Davids MS, Anderson MA, Beaven AW, Rosen ST, Tam CS, Prine B, Agarwal SK, Munasinghe W, Zhu M, Lash LL, Desai M, Cerri E, Verdugo M, Kim SY, Humerickhouse RA, Gordon GB, Kipps TJ, Roberts AW
Institution:Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Victorian Comprehensive Cancer Centre, Parkville, Melbourne, VIC, Australia; Faculty of Medicine, University of Melbourne, Parkville, Melbourne, VIC, Australia. Electronic address:; Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Duke University Medical Center, Durham, NC, USA.; University of California San Diego, San Diego, CA, USA.; Hofstra Northwell School of Medicine, Hempstead, NY, USA.
Journal:Lancet Oncol. 2017 Feb;18(2):230-240. doi: 10.1016/S1470-2045(17)30012-8. Epub 2017 Jan 13.

18:Front-line treatment of CLL in the era of novel agents.
Authors:Robak T, Stilgenbauer S, Tedeschi A
Institution:Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, 93-510 Lodz, ul. Ciolkowskiego 2, Poland. Electronic address: Ulm 89081, Germany. Electronic address: Ospedale Maggiore 3, 20162 Milano, Italy. Electronic address:
Journal:Cancer Treat Rev. 2017 Feb;53:70-78. doi: 10.1016/j.ctrv.2016.12.007. Epub 2016 Dec 30.

19:Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial.
Authors:Sharman JP, Farber CM, Mahadevan D, Schreeder MT, Brooks HD, Kolibaba KS, Fanning S, Klein L, Greenwald DR, Sportelli P, Miskin HP, Weiss MS, Burke JM
Institution:Willamette Valley Cancer Institute, Springfield, OR, USA. USA.
Journal:Br J Haematol. 2017 Feb;176(3):412-420. doi: 10.1111/bjh.14447. Epub 2016 Dec 16.

20:Randomized phase 2 study of otlertuzumab and bendamustine versus bendamustine in patients with relapsed chronic lymphocytic leukaemia.
Authors:Robak T, Hellmann A, Kloczko J, Loscertales J, Lech-Maranda E, Pagel JM, Mato A, Byrd JC, Awan FT, Hebart H, Garcia-Marco JA, Hill BT, Hallek M, Eisenfeld AJ, Stromatt SC, Jaeger U
Institution:Department of Haematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland. Warsaw, Poland. Medical Education, Warsaw, Poland. USA. Philadelphia, PA, USA. Mutlangen, Germany. Cleveland Clinic, Cleveland, OH, USA. of Excellence on Cellular Stress Responses in Aging (CECAD) University of Cologne, Cologne, Germany. University of Vienna, Vienna, Austria.
Journal:Br J Haematol. 2017 Feb;176(4):618-628. doi: 10.1111/bjh.14464. Epub 2016 Dec 15.

21:The safety profile of monoclonal antibodies for chronic lymphocytic leukemia.
Authors:Korycka-Wolowiec A, Wolowiec D, Robak T
Institution:a Department of Hematology Medical , University of Lodz , Lodz , Poland.
Journal:Expert Opin Drug Saf. 2017 Feb;16(2):185-201. doi: 10.1080/14740338.2017.1264387. Epub 2016 Dec 4.

22:Alemtuzumab consolidation in chronic lymphocytic leukaemia: a phase I/II multicentre trial.
Authors:Al-Sawaf O, Fischer K, Herling CD, Ritgen M, Bottcher S, Bahlo J, Elter T, Stilgenbauer S, Eichhorst BF, Busch R, Elberskirch U, Abenhardt W, Kneba M, Hallek M, Wendtner CM
Institution:Department I of Internal Medicine and Center of Integrated Oncology Cologne-Bonn, German CLL Study group, University of Cologne, Cologne, Germany.; Department II of Internal Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.; Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany.; Institute for Medical Statistic and Epidemiology, Technical University, Munich, Germany.; MOP Elisenhof, Munich, Germany.
Journal:Eur J Haematol. 2017 Mar;98(3):254-262. doi: 10.1111/ejh.12825. Epub 2016 Dec 1.

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