Chronic Lymphocytic Leukemia
September 2021 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:Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia.
Authors:Parry H, McIlroy G, Bruton R, Ali M, Stephens C, Damery S, Otter A, McSkeane T, Rolfe H, Faustini S, Wall N, Hillmen P, Pratt G, Paneesha S, Zuo J, Richter A, Moss P
Institution:Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK. 2TT, UK. 2TT, UK. 2TT, UK. 2TT, UK. UK. UK. Birmingham, UK. Birmingham, UK. 2TT, UK. 2TT, UK. UK. East, B9 5SS, Birmingham, UK.
Journal:Blood Cancer J. 2021 Jul 30;11(7):136. doi: 10.1038/s41408-021-00528-x.

2:An update on acalabrutinib to treat chronic lymphocytic leukemia.
Authors:Blackmon A, O'Brien S
Institution:Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, California, USA. Irvine, California, USA. California, USA.
Journal:Drugs Today (Barc). 2021 Jul;57(7):417-431. doi: 10.1358/dot.2021.57.7.3285932.

3:Current State of CAR T-Cell Therapy in Chronic Lymphocytic Leukemia.
Authors:Mancikova V, Smida M
Institution:Central European Institute of Technology (CEITEC), Masaryk University, 62500 Brno, Czech Republic.
Journal:Int J Mol Sci. 2021 May 24;22(11):5536. doi: 10.3390/ijms22115536.

4:Current and emerging investigational venetoclax-based therapies in chronic lymphocytic leukemia.
Authors:Molica S, Allsup D, Gianfelici V, Levato L, Aiello V, Bailey J, Polliack A
Institution:Department Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro,Italy.
Journal:Expert Opin Investig Drugs. 2021 Jun;30(6):621-633. doi: 10.1080/13543784.2021.1924669. Epub 2021 May 15.

5:Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia.
Authors:Herishanu Y, Avivi I, Aharon A, Shefer G, Levi S, Bronstein Y, Morales M, Ziv T, Shorer Arbel Y, Scarfò L, Joffe E, Perry C, Ghia P
Institution:Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Division of Experimental Oncology, Universita Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy.
Journal:Blood. 2021 Jun 10;137(23):3165-3173. doi: 10.1182/blood.2021011568.

6:Efficacy of idelalisib and rituximab in relapsed/refractory chronic lymphocytic leukemia treated outside of clinical trials. A report of the Gimema Working Group.
Authors:Rigolin GM, Cavazzini F, Piciocchi A, Arena V, Visentin A, Reda G, Zamprogna G, Cibien F, Vitagliano O, Coscia M, Farina L, Gaidano G, Murru R, Varettoni M, Paolini R, Sportoletti P, Pietrasanta D, Molinari AL, Quaglia FM, Laurenti L, Marasca R, Marchetti M, Mauro FR, Crea E, Vignetti M, Gentile M, Montillo M, Foà R, Cuneo A
Institution:Department of Medical Sciences, Hematology Section, University of Ferrara, Cona - Ferrara, Italy. Ferrara, Italy. Padua, Padua, Italy. Milan, Italy. Milan, Italy. Turin, Italy. Italy. Milano, Italy. Piemonte Orientale, Novara, Italy. "G. Brotzu", Cagliari, Italy. Hemato-Oncological Research, Ospedale S. Maria della Misericordia, Perugia, Italy. Ospedale civile SS Antonio e Biagio, Alessandria, Italy. Modena and Reggio Emilia, Modena, Italy. University, Rome, Italy. Milan, Italy. University, Rome, Italy. Ferrara, Italy.
Journal:Hematol Oncol. 2021 Aug;39(3):326-335. doi: 10.1002/hon.2861. Epub 2021 Mar 26.

7:Overall survival, adverse events, and economic burden in patients with chronic lymphocytic leukemia receiving systemic therapy: Real-world evidence from the medicare population.
Authors:Goyal RK, Nagar SP, Kabadi SM, Le H, Davis KL, Kaye JA
Institution:RTI Health Solutions, Research Triangle Park, NC, USA.
Journal:Cancer Med. 2021 Apr;10(8):2690-2702. doi: 10.1002/cam4.3855. Epub 2021 Mar 18.

8:Venetoclax as a therapeutic option for the treatment of chronic lymphocytic leukemia: the evidence so far.
Authors:Held L, Siu C, Shadman M
Institution:School of Pharmacy, University of Washington, Seattle, WA, USA.
Journal:Expert Opin Pharmacother. 2021 Apr;22(6):655-665. doi: 10.1080/14656566.2021.1882421. Epub 2021 Feb 27.

9:Ublituximab plus ibrutinib versus ibrutinib alone for patients with relapsed or refractory high-risk chronic lymphocytic leukaemia (GENUINE): a phase 3, multicentre, open-label, randomised trial.
Authors:Sharman JP, Brander DM, Mato AR, Ghosh N, Schuster SJ, Kambhampati S, Burke JM, Lansigan F, Schreeder MT, Lunin SD, Zweibach A, Shtivelband M, Travis PM, Chandler JC, Kolibaba KS, Sportelli P, Miskin HP, Weiss MS, Flinn IW
Institution:Willamette Valley Cancer Institute, US Oncology Research, Eugene, OR, USA. Electronic address: Sarah Cannon Research Institute, Nashville, TN, USA.
Journal:Lancet Haematol. 2021 Apr;8(4):e254-e266. doi: 10.1016/S2352-3026(20)30433-6. Epub 2021 Feb 22.

10:Randomized controlled trial of individualized, low dose, fixed duration lenalidomide maintenance versus observation after frontline chemo-immunotherapy in CLL.
Authors:Jindal N, Lad DP, Malhotra P, Prakash G, Khadwal A, Jain A, Sachdeva MS, Sreedharanunni S, Naseem S, Varma N, Varma S
Institution:Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Journal:Leuk Lymphoma. 2021 Jul;62(7):1674-1681. doi: 10.1080/10428194.2021.1885668. Epub 2021 Feb 21.

11:Outcomes in chronic lymphocytic leukemia patients on novel agents in the US Veterans Health Administration System.
Authors:Frei CR, Le H, McHugh D, Ryan K, Jones X, Galley S, Franklin K, Baus CJ, Tavera J, Janania-Martinez M, Gregorio D, Ananth S, Uribe R, Surapaneni P, Espinoza-Gutarra M, Song MM, Teng C, Obodozie-Ofoegbu OO, Nooruddin Z
Institution:South Texas Veterans Health Care System, San Antonio, TX, USA. USA. USA. USA. University of South Carolina, Columbia, SC, USA. USA. USA.
Journal:Leuk Lymphoma. 2021 Jul;62(7):1664-1673. doi: 10.1080/10428194.2021.1876863. Epub 2021 Feb 11.

12:Real-world outcomes following venetoclax therapy in patients with chronic lymphocytic leukemia or Richter syndrome: a FILO study of the French compassionate use cohort.
Authors:Bouclet F, Calleja A, Dilhuydy MS, Véronèse L, Pereira B, Amorim S, Cymbalista F, Herbaux C, de Guibert S, Roos-Weil D, Hivert B, Aurran T, Dupuis J, Blouet A, Tchernonog E, Laribi K, Dmytruck N, Morel P, Michallet AS, Dartigeas C, Tournilhac O, Nguyen-Khac F, Delmer A, Feugier P, Ysebaert L, Guièze R
Institution:Service d'Hematologie clinique adultes et therapie cellulaire, Hopital Estaing, CHU Clermont-Ferrand, 1 place Lucie Aubrac, 63000, Clermont-Ferrand, France.
Journal:Ann Hematol. 2021 Apr;100(4):987-993. doi: 10.1007/s00277-021-04419-w. Epub 2021 Jan 25.

13:EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia.
Authors:Delgado J, Josephson F, Camarero J, Garcia-Ochoa B, Lopez-Anglada L, Prieto-Fernandez C, van Hennik PB, Papadouli I, Gisselbrecht C, Enzmann H, Pignatti F
Institution:Oncology and Hematology Office, European Medicines Agency, Amsterdam, The Netherlands.
Journal:Oncologist. 2021 Mar;26(3):242-249. doi: 10.1002/onco.13685. Epub 2021 Feb 10.

14:Acalabrutinib: a highly selective, potent Bruton tyrosine kinase inhibitor for the treatment of chronic lymphocytic leukemia.
Authors:Ghia P, Dlugosz-Danecka M, Scarfò L, Jurczak W
Institution:Division of Experimental Oncology, Strategic Research Program on Chronic Lymphocytic Leukemia, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy. Department of Lymphoid Malignancies, Maria Sk?odowska-Curie National Research Institute of Oncology, Krakow, Poland.
Journal:Leuk Lymphoma. 2021 May;62(5):1066-1076. doi: 10.1080/10428194.2020.1864352. Epub 2021 Jan 11.

15:Comparison of ibrutinib and idelalisib plus rituximab in real-life relapsed/resistant chronic lymphocytic leukemia cases.
Authors:Morabito F, Tripepi G, Del Poeta G, Mauro FR, Reda G, Sportoletti P, Laurenti L, Coscia M, Herishanu Y, Bossio S, Varettoni M, Murru R, Chiarenza A, Visentin A, Condoluci A, Moia R, Pietrasanta D, Loseto G, Consoli U, Scortechini I, Rossi FM, Zucchetto A, Al-Janazreh H, Vigna E, Martino EA, Mendicino F, Cassin R, D'Arrigo G, Galimberti S, Rago A, Angeletti I, Biagi A, Del Giudice I, Bomben R, Neri A, Fronza G, Monti P, Menichini P, Cutrona G, Jaksic O, Rossi D, Di Raimondo F, Cuneo A, Gaidano G, Polliack A, Trentin L, Foà R, Ferrarini M, Gattei V, Gentile M
Institution:Biothecnology Research Unit, AO of Cosenza, Cosenza, Italy. Victoria Hospital, East Jerusalem, Israel. Italy. Italy. Italy. Tel-Aviv University, Tel-Aviv, Israel. University of Catania, Catania, Italy. Padova, Padova, Italy. Piedmont, Novara, Italy. Alessandria, Italy. Italy. Aviano (CRO) IRCCS, Aviano, Italy. Aviano (CRO) IRCCS, Aviano, Italy. Victoria Hospital, East Jerusalem, Israel. of Pisa, Pisa, Italy. Italy. Italy. Aviano (CRO) IRCCS, Aviano, Italy. Genoa, Italy. Genoa, Italy. Genoa, Italy. University of Catania, Catania, Italy. Italy. Piedmont, Novara, Italy. Israel. Padova, Padova, Italy. Italy. Aviano (CRO) IRCCS, Aviano, Italy.
Journal:Eur J Haematol. 2021 Apr;106(4):493-499. doi: 10.1111/ejh.13573. Epub 2021 Jan 28.

16:First-line treatments for chronic lymphocytic leukemia: Analysis of 7 trials based on the restricted mean survival time.
Authors:Bartoli L, Ferracane E, Trippoli S, Messori A
Journal:Int J Clin Pharmacol Ther. 2021 Apr;59(4):322-327. doi: 10.5414/CP203852.

17:A phase II Japanese trial of fludarabine, cyclophosphamide and rituximab for previously untreated chronic lymphocytic leukemia.
Authors:Izutsu K, Kinoshita T, Takizawa J, Fukuhara S, Yamamoto G, Ohashi Y, Suzumiya J, Tobinai K
Institution:Department of Hematology, Toranomon Hospital, Tokyo, Japan. Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
Journal:Jpn J Clin Oncol. 2021 Mar 3;51(3):408-415. doi: 10.1093/jjco/hyaa215.

18:Phase 2, multicenter GIBB study of obinutuzumab plus bendamustine in previously untreated patients with chronic lymphocytic leukemia.
Authors:Sharman JP, Burke JM, Yimer HA, Boxer MA, Babu S, Li J, Mun Y, Danilov AV
Institution:Willamette Valley Cancer Institute and Research Center, US Oncology Research, Eugene, OR, USA. Oregon Health and Science University, Portland, OR, USA.
Journal:Leuk Lymphoma. 2021 Apr;62(4):791-800. doi: 10.1080/10428194.2020.1850719. Epub 2020 Nov 26.

19:Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party.
Authors:Schetelig J, Chevallier P, van Gelder M, Hoek J, Hermine O, Chakraverty R, Browne P, Milpied N, Malagola M, Socié G, Delgado J, Deconinck E, Damaj G, Maury S, Beelen D, Quoc SN, Shankara P, Brecht A, Mayer J, Hunault-Berger M, Bittenbring J, Thieblemont C, Lepretre S, Baldauf H, de Wreede LC, Tournilhac O, Yakoub-Agha I, Kröger N, Dreger P
Institution:Medical Clinic I, University Hospital, Dresden, Germany. University of Paris, Paris, France. London Hospital, London, UK. Brescia, Italy. Caen, France. Créteil, France. University, Rouen, France. Leiden, The Netherlands. Universitaire, Clermont Ferrand, France. Lille, France.
Journal:Bone Marrow Transplant. 2021 Mar;56(3):605-613. doi: 10.1038/s41409-020-01069-w. Epub 2020 Oct 2.

20:A phase 1b/2 study of duvelisib in combination with FCR (DFCR) for frontline therapy for younger CLL patients.
Authors:Davids MS, Fisher DC, Tyekucheva S, McDonough M, Hanna J, Lee B, Francoeur K, Montegaard J, Odejide O, Armand P, Arnason J, Brown JR
Institution:Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. USA. USA.
Journal:Leukemia. 2021 Apr;35(4):1064-1072. doi: 10.1038/s41375-020-01010-6. Epub 2020 Aug 20.

21:Patterns of use and safety of ibrutinib in real-life practice.
Authors:Allouchery M, Tomowiak C, Guidez S, Delwail V, Delaunay P, Lafay-Chebassier C, Salvo F, Pérault-Pochat MC
Institution:Pharmacologie Clinique et Vigilances, CHU de Poitiers, Poitiers, France. de Poitiers, Poitiers, France. INSERM U1219, Université de Bordeaux, Bordeaux, France. de Poitiers, Poitiers, France.
Journal:Br J Clin Pharmacol. 2021 Mar;87(3):895-904. doi: 10.1111/bcp.14440. Epub 2020 Jul 5.

22:Response to the conjugate pneumococcal vaccine (PCV13) in patients with chronic lymphocytic leukemia (CLL).
Authors:Mauro FR, Giannarelli D, Galluzzo CM, Vitale C, Visentin A, Riemma C, Rosati S, Porrazzo M, Pepe S, Coscia M, Trentin L, Gentile M, Raponi S, Micozzi A, Gentile G, Baroncelli S
Institution:Hematology, Department of Translational and Precision Medicine, 'Sapienza' University, Rome, Italy. Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy. Padua, Padua, Italy. University, Rome, Italy. University, Rome, Italy. University, Rome, Italy. University, Rome, Italy. Department of Molecular Biotechnology and Health Sciences, University of Turin, Torino, Italy.
Journal:Leukemia. 2021 Mar;35(3):737-746. doi: 10.1038/s41375-020-0884-z. Epub 2020 Jun 17.

23:Allogeneic hematopoietic cell transplantation is an effective treatment for patients with Richter syndrome: A systematic review and meta-analysis.
Authors:Aulakh S, Reljic T, Yassine F, Ayala E, Chavez JC, Chanan-Khan A, Pinilla-Ibarz J, Kumar A, Kharfan-Dabaja MA
Institution:Division of Hematology-Oncology, West Virginia University, Morgantown, WV, USA. University of South Florida, Tampa, FL, USA. Clinic, Jacksonville, FL, USA. Clinic, Jacksonville, FL, USA. University of South Florida, Tampa, FL, USA. Clinic, Jacksonville, FL, USA. Electronic address:
Journal:Hematol Oncol Stem Cell Ther. 2021 Mar;14(1):33-40. doi: 10.1016/j.hemonc.2020.05.002. Epub 2020 May 15.

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"I was recently diagnosed with CLL and searched all over the Web for information. I found the MediFocus Guidebook on Chronic Lymphocytic Leukemia to be a very useful resource. The information about chemotherapy was most important to me as well as recent studies concerning general treatments for this condition. The most valuable information was contained in the extensive references listed which were easy to access with a simple 'mouse' click. You are welcome to use my name as a reference."
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