Chronic Lymphocytic Leukemia
July 2023 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:First line therapy of CLL.
Authors:Hallek M
Institution:Department I of Internal Medicine, University of Cologn, Cologne, Germany.
Journal:Hematol Oncol. 2023 Jun;41 Suppl 1:129-135. doi: 10.1002/hon.3145.

2:Obinutuzumab plus bendamustine for relapsed/refractory chronic lymphocytic leukemia and predictive and prognostic impact of genetic alterations: the phase II GABRIELL study.
Authors:Bravo J, Baltasar Tello P, González Garcia E, Ríos Herranz E, Páyer AR, Terol Castera MJ, Champ D, Medina Perez A, Gironella M, Fernández Zarzoso M, Forés R, Delgado J, Garcia-Marco JA
Institution:Molecular Cytogenetics Unit, Hematology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Journal:Leuk Lymphoma. 2023 May;64(5):913-926. doi: 10.1080/10428194.2023.2216327. Epub 2023 May 31.

3:First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia.
Authors:Eichhorst B, Niemann CU, Kater AP, Fürstenau M, von Tresckow J, Zhang C, Robrecht S, Gregor M, Juliusson G, Thornton P, Staber PB, Tadmor T, Lindström V, da Cunha-Bang C, Schneider C, Poulsen CB, Illmer T, Schöttker B, Nösslinger T, Janssens A, Christiansen I, Baumann M, Frederiksen H, van der Klift M, Jäger U, Leys MBL, Hoogendoorn M, Lotfi K, Hebart H, Gaska T, Koene H, Enggaard L, Goede J, Regelink JC, Widmer A, Simon F, De Silva N, Fink AM, Bahlo J, Fischer K, Wendtner CM, Kreuzer KA, Ritgen M, Brüggemann M, Tausch E, Levin MD, van Oers M, Geisler C, Stilgenbauer S, Hallek M
Institution:From the Department I of Internal Medicine, Center for Integrated Oncology Aachen-Bonn-Cologne-Dusseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne (B.E., M.F., C.Z., S.R., F.S., A.-M.F., J.B., K.F., K.A.K., M. Hallek), the Clinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen (J.T.), the Division of Chronic Lymphocytic Leukemia, Department of Internal Medicine III, University of Ulm, Ulm (C.S., E.T., S.S.), Group Practice for Hematology and Oncology, Dresden (T.I.); the Hematology-Oncology Center, Wurzburg (B.S.), Specialist Medical Practice of Hematology and Oncology, Mutlangen (H.H.), the Department of Hematology, Clinic for Hematology and Oncology, Centrum of Oncology, Bruderhospital St. Josef, Paderborn (T.G.), the Munich Clinic Schwabing, Academic Teaching Hospital, Ludwig Maximilian University, Munich (C.-M.W.); and the Department of Hematology, Univ
Journal:N Engl J Med. 2023 May 11;388(19):1739-1754. doi: 10.1056/NEJMoa2213093.

4:Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial.
Authors:Hillmen P, Pitchford A, Bloor A, Broom A, Young M, Kennedy B, Walewska R, Furtado M, Preston G, Neilson JR, Pemberton N, Sidra G, Morley N, Cwynarski K, Schuh A, Forconi F, Elmusharaf N, Paneesha S, Fox CP, Howard DR, Hockaday A, Brown JM, Cairns DA, Jackson S, Greatorex N, Webster N, Shingles J, Dalal S, Patten PEM, Allsup D, Rawstron A, Munir T
Institution:Leeds Cancer Centre, Leeds Teaching Hospitals Trust, Leeds, UK. Electronic address:
Journal:Lancet Oncol. 2023 May;24(5):535-552. doi: 10.1016/S1470-2045(23)00144-4.

5:Practical Management of Richter Transformation in 2023 and Beyond.
Authors:Ryan CE, Davids MS
Institution:Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Journal:Am Soc Clin Oncol Educ Book. 2023 Jan;43:e390804. doi: 10.1200/EDBK_390804.

6:Ofatumumab regimens in chronic lymphocytic leukemia: a meta-analysis.
Authors:Ashoub MH, Naseri A, Mohammadi P, Mohammadi M
Institution:Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.; Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran.
Journal:Ann Hematol. 2023 Jun;102(6):1301-1306. doi: 10.1007/s00277-023-05246-x. Epub 2023 May 3.

7:Should treatment of hypogammaglobulinemia with immunoglobulin replacement therapy (IgRT) become standard of care in patients with chronic lymphocytic leukemia?
Authors:Noto A, Cassin R, Mattiello V, Bortolotti M, Reda G, Barcellini W
Institution:Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Journal:Front Immunol. 2023 Apr 14;14:1062376. doi: 10.3389/fimmu.2023.1062376. eCollection 2023.

8:Challenges and opportunities of CAR T-cell therapies for CLL.
Authors:Zhao Z, Grégoire C, Oliveira B, Chung K, Melenhorst JJ
Institution:Cell Therapy & Immuno-Engineering Program, Center for ImmunoTherapy and Precision Immuno-Oncology, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH. Electronic address:
Journal:Semin Hematol. 2023 Jan;60(1):25-33. doi: 10.1053/j.seminhematol.2023.01.002. Epub 2023 Feb 8.

9:Current therapies for chronic lymphocytic leukemia: risk and prophylaxis strategies for secondary/opportunistic infections.
Authors:Diella L, Bavaro DF, Loseto G, Pasciolla C, Minoia C, Di Gennaro D, Belati A, De Candia MS, Di Gennaro F, Saracino A, Guarini A
Institution:Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari 'Aldo Moro', Bari, Italy.; IRCCS Istituto Tumori 'Giovanni Paolo II', Hematology Unit, Bari, Italy.
Journal:Expert Rev Hematol. 2023 Apr;16(4):267-276. doi: 10.1080/17474086.2023.2192918. Epub 2023 Apr 10.

10:The Impact of Improved Treatments on Survival of Adult U.S. Leukemia Patients: 1990-2018.
Authors:Howlader N, Sharon E, Bhattacharya M, Ehrlich LA, Richardson NC, Gormley NJ, de Claro RA, Wood AE, Mariotto AB, Cronin KA
Institution:Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland.
Journal:Cancer Epidemiol Biomarkers Prev. 2023 Jun 1;32(6):744-747. doi: 10.1158/1055-9965.EPI-22-1171.

11:Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review.
Authors:Shadman M
Institution:Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington.
Journal:JAMA. 2023 Mar 21;329(11):918-932. doi: 10.1001/jama.2023.1946.

12:SOHO State of the Art Updates and Next Questions | Infections in Chronic Lymphocytic Leukemia Patients: Risks and Management.
Authors:Gargiulo E, Ribeiro EFO, Niemann CU
Institution:Tumor-Stroma Interactions, Department of Oncology, Luxembourg Institute of Health, Luxembourg City, Luxembourg; Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; PERSIMUNE, Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.; Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; Center of Oncology and Hematology, Hospital Santa Lucia Sul, Brasilia, Brazil; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Electronic address:
Journal:Clin Lymphoma Myeloma Leuk. 2023 May;23(5):322-332. doi: 10.1016/j.clml.2023.02.001. Epub 2023 Feb 10.

13:Real-World Clinical Outcomes and Adverse Events in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Single-Center Retrospective Study.
Authors:Moldovianu AM, Stoia R, Vasilica M, Ursuleac I, Badelita SN, Tomescu AA, Preda OD, Bardas A, Cirstea M, Coriu D
Institution:Department of Hematology and Bone Marrow Transplant, Fundeni Clinical Institute, 022328 Bucharest, Romania.
Journal:Medicina (Kaunas). 2023 Feb 9;59(2):324. doi: 10.3390/medicina59020324.

14:SOHO State of the Art Updates and Next Questions: New Targetable Pathways in Chronic Lymphocytic Leukemia.
Authors:Fakhri B, Danilov A
Institution:Division of Hematology, Department of Medicine, Stanford University, Palo Alto, CA.; Department of Hematology and Hematopoietic Stem Cell Transplant, City of Hope National Medical Center, Duarte, CA. Electronic address:
Journal:Clin Lymphoma Myeloma Leuk. 2023 Apr;23(4):232-237. doi: 10.1016/j.clml.2023.01.009. Epub 2023 Jan 20.

15:Managing Ibrutinib-Intolerant Patients With B-Cell Malignancies.
Authors:Muñoz J, Sarosiek S, Castillo JJ
Institution:Division of Hematology and Oncology, Mayo Clinic, Phoenix, AZ, USA.; Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Journal:Oncologist. 2023 Apr 6;28(4):309-318. doi: 10.1093/oncolo/oyac260.

16:Risk of second primary malignancies in patients with chronic lymphocytic leukemia: a population-based study in the Netherlands, 1989-2019.
Authors:van der Straten L, Levin MD, Dinnessen MAW, Visser O, Posthuma EFM, Doorduijn JK, Langerak AW, Kater AP, Dinmohamed AG
Institution:Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands.
Journal:Blood Cancer J. 2023 Jan 13;13(1):15. doi: 10.1038/s41408-023-00784-z.

17:Canadian evidence-based guideline for frontline treatment of chronic lymphocytic leukemia: 2022 update.
Authors:Owen C, Banerji V, Johnson N, Gerrie A, Aw A, Chen C, Robinson S
Institution:Division of Hematology and Hematological Malignancies, Foothills Medical Centre, Calgary, AB T2N 4N2, Canada. Electronic address:; Division of Hematology, Dalhousie University, and qeii Health Sciences Centre, Halifax, NS B3H 2Y9, Canada.
Journal:Leuk Res. 2023 Feb;125:107016. doi: 10.1016/j.leukres.2023.107016. Epub 2023 Jan 5.

18:Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia.
Authors:Brown JR, Eichhorst B, Hillmen P, Jurczak W, Kaźmierczak M, Lamanna N, O'Brien SM, Tam CS, Qiu L, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Salmi T, Wang MD, Fu L, Li J, Wu K, Cohen A, Shadman M
Institution:From the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston (J.R.B.); the Department of Internal Medicine, University of Cologne, Center for Integrated Oncology Aachen Bonn Koln Dusseldorf, Cologne, Germany (B.E.); St. James's University Hospital, Leeds, United Kingdom (P.H.); Maria Sk?odowska-Curie National Research Institute of Oncology, Krakow (W.J.), the Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan (M.K.), the Department of Hematology and Cancer Prevention, Faculty of Health Sciences, Medical University of Silesia, Katowice (S.G.), the Department of Hematology and Transplantology, Medical University of Gda?sk, Gda?sk (A.M.), and the Medical University of Lodz, Lodz (T.R.) - all in Poland; Herbert Irving Comprehensive Cancer Center, Columbia University, New York (N.L.); Chao Family Comprehensive Cancer Center, University of California, Irvine (S.M.O.), and BeiGene USA, San Mateo (T.S., M.-D.-Y.W., L.F., J.L.
Journal:N Engl J Med. 2023 Jan 26;388(4):319-332. doi: 10.1056/NEJMoa2211582. Epub 2022 Dec 13.

19:Immunotherapy combinations for chronic lymphocytic leukemia: advantages and disadvantages.
Authors:Robak P, Robak T
Institution:Department of Experimental Hematology, Medical University of Lodz, ?od?, Poland.; Department of Hematology, Medical University of Lodz, ?od?, Poland.
Journal:Expert Opin Biol Ther. 2023 Jan;23(1):21-35. doi: 10.1080/14712598.2022.2145881. Epub 2022 Nov 17.

20:Vaccination efficacy in patients with chronic lymphocytic leukemia.
Authors:Wang KY, Shah P, Skavla B, Fayaaz F, Chi J, Rhodes JM
Institution:Department of Internal Medicine, Northwell Health, Manhasset, NY, USA.; Department of Hematology Oncology, Northwell Health, Manhasset, NY, USA.
Journal:Leuk Lymphoma. 2023 Jan;64(1):42-56. doi: 10.1080/10428194.2022.2133538. Epub 2022 Oct 21.

21:Patient characteristics that predict Richter's transformation in patients with chronic lymphocytic leukemia treated with ibrutinib.
Authors:Kittai AS, Huang Y, Beckwith KA, Bhat SA, Bond DA, Byrd JC, Goldstein D, Grever MR, Miller C, Rogers KA, Yano M, Woyach JA
Institution:Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, Ohio, USA.
Journal:Am J Hematol. 2023 Jan;98(1):56-65. doi: 10.1002/ajh.26755. Epub 2022 Oct 20.

22:Emerging Therapies for the Management of Richter Transformation.
Authors:Smyth E, Eyre TA, Cheah CY
Institution:Department of Haematology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
Journal:J Clin Oncol. 2023 Jan 10;41(2):395-409. doi: 10.1200/JCO.22.01028. Epub 2022 Sep 21.

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