Chronic Lymphocytic Leukemia (CLL) Questions & Answers

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2. Hallek M, Al-Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am J Hematol. 2021 Dec 1. 96 (12):1679-1705. [QxMD MEDLINE Link].

3. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018 Jun 21. 131 (25):2745-2760. [QxMD MEDLINE Link].

4. PDQ Adult Treatment Editorial Board. Chronic Lymphocytic Leukemia Treatment (PDQ®): Health Professional Version. PDQ Cancer Information Summaries. Bethesda, MD: National Cancer Institute; February 25, 2022. [Full Text].

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6. Klepfish A, Gilles L, Ioannis K, Eliezer R, Ami S. Enhancing the action of rituximab in chronic lymphocytic leukemia by adding fresh frozen plasma: complement/rituximab interactions & clinical results in refractory CLL. Ann N Y Acad Sci. 2009 Sep. 1173:865-73. [QxMD MEDLINE Link].

7. Badoux XC, Keating MJ, Wang X, et al. Fludarabine, cyclophosphamide and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. Blood. 2011 Jan 18. [QxMD MEDLINE Link].

8. Shanafelt TD, Wang XV, Kay NE, Hanson CA, O'Brien S, Barrientos J, et al. Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. N Engl J Med. 2019 Aug 1. 381 (5):432-443. [QxMD MEDLINE Link].

9. Zenz T, Benner A, Duhrsen U, Durig J, Dohner H, Siffert W, et al. BCL2-938C>A polymorphism and disease progression in chronic lymphocytic leukemia. Leuk Lymphoma. 2009 Sep 11. 1-6. [QxMD MEDLINE Link].

10. Nicoloso MS, Kipps TJ, Croce CM, Calin GA. MicroRNAs in the pathogeny of chronic lymphocytic leukaemia. Br J Haematol. 2007 Dec. 139(5):709-16. [QxMD MEDLINE Link]. [Full Text].

11. Hanlon K, Rudin CE, Harries LW. Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL). PLoS One. 2009 Sep 25. 4(9):e7169. [QxMD MEDLINE Link]. [Full Text].

12. Fabbri M, Bottoni A, Shimizu M, et al. Association of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia. JAMA. 2011 Jan 5. 305(1):59-67. [QxMD MEDLINE Link].

13. Wang L, Lawrence MS, Wan Y, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 2011 Dec 29. 365(26):2497-506. [QxMD MEDLINE Link]. [Full Text].

14. Malcovati L, Stevenson K, Papaemmanuil E, et al. SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS. Blood. 2020;136(2):157-170. Blood. 2021 May 27. 137 (21):3003. [QxMD MEDLINE Link]. [Full Text].

15. Slager SL, Kay NE. Familial Chronic Lymphocytic Leukemia: What Does it Mean to Me?. Clin Lymphoma Myeloma. 2009 Sep 1. 9:S194-S197. [QxMD MEDLINE Link].

16. Berndt SI, Camp NJ, Skibola CF, Vijai J, Wang Z, et al. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia. Nat Commun. 2016 Mar 9. 7:10933. [QxMD MEDLINE Link].

17. Cancer Facts & Figures 2023. American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2023/2023-cancer-facts-and-figures.pdf. Accessed: January 12, 2023.

18. Cancer Stat Facts: Leukemia — Chronic Lymphocytic Leukemia (CLL). National Cancer Institute Surveillance, Epidemiology, and End Results Program. Available at https://seer.cancer.gov/statfacts/html/clyl.html. Accessed: January 12, 2023.

19. Benintende G, Innocenti I, Fresa A, Autore F, Tomasso A, Piciocchi A, et al. Clinical and molecular features of familial chronic lymphocytic leukemia: a pilot monocentric study. Haematologica. 2022 Dec 22. [QxMD MEDLINE Link].

20. Rai KR, Barrientos JC. Chronic lymphocytic leukemia. Bast RC Jr, Croce CM, Hait WN, et al, eds. Holland-Frei Cancer Medicine. 9th ed. Hoboken, NJ: John Wiley & Sons, Inc; 2017. 1595-1604.

21. Kristinsson SY, Dickman PW, Wilson WH, et al. Improved survival in chronic lymphocytic leukemia in the past decade: a population-based study including 11,179 patients diagnosed between 1973-2003 in Sweden. Haematologica. 2009 Sep. 94(9):1259-65. [QxMD MEDLINE Link]. [Full Text].

22. Jacque N, Leblond V. [Chronic lymphocytic leukemia]. Presse Med. 2019 Jul-Aug. 48 (7-8 Pt 1):807-815. [QxMD MEDLINE Link].

23. Maurer MJ, Cerhan JR, Katzmann JA, et al. Monoclonal and polyclonal serum free light chains and clinical outcome in chronic lymphocytic leukemia. Blood. 2011 Sep 8. 118(10):2821-6. [QxMD MEDLINE Link]. [Full Text].

24. Clay-Gilmour AI, Rishi AR, Goldin LR, et. al. Association of elevated serum free light chains with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. Blood Cancer J. 2019 Aug 5. 9 (8):59. [QxMD MEDLINE Link].

25. [Guideline] Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018 Jun 21. 131 (25):2745-2760. [QxMD MEDLINE Link]. [Full Text].

26. Bouley J, Deriano L, Delic J, Merle-Béral H. New molecular markers in resistant B-CLL. Leuk Lymphoma. 2006 May. 47(5):791-801. [QxMD MEDLINE Link].

27. Parikh SA, Strati P, Tsang M, West CP, Shanafelt TD. Should IGHV status and FISH testing be performed in all CLL patients at diagnosis? A systematic review and meta-analysis. Blood. 2016 Feb 3. 39 (8A):935-7. [QxMD MEDLINE Link].

28. Hillmen P, Skotnicki AB, Robak T, et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007 Dec 10. 25(35):5616-23. [QxMD MEDLINE Link].

29. Montillo M, Tedeschi A, Miqueleiz S, et al. Alemtuzumab as consolidation after a response to fludarabine is effective in purging residual disease in patients with chronic lymphocytic leukemia. J Clin Oncol. 2006 May 20. 24(15):2337-42. [QxMD MEDLINE Link]. [Full Text].

30. Moreton P, Kennedy B, Lucas G, et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol. 2005 May 1. 23(13):2971-9. [QxMD MEDLINE Link]. [Full Text].

31. Visone R, Veronese A, Rassenti LZ, et al. miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia. Blood. 2011 Sep 15. 118(11):3072-9. [QxMD MEDLINE Link]. [Full Text].

32. International CLL-IPI working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016 Jun. 17 (6):779-790. [QxMD MEDLINE Link].

33. Bosch F, Ferrer A, Villamor N, et al. Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication. Clin Cancer Res. 2008 Jan 1. 14(1):155-61. [QxMD MEDLINE Link].

34. Byrd JC, Gribben JG, Peterson BL, et al. Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol. 2006 Jan 20. 24(3):437-43. [QxMD MEDLINE Link].

35. Seymour JF. CLL12: a positive answer to a poorly phrased question. Blood. 2022 Jan 13. 139 (2):151-152. [QxMD MEDLINE Link]. [Full Text].

36. Wierda WG, O'Brien S, Wang X, et al. Multivariable model for time to first treatment in patients with chronic lymphocytic leukemia. J Clin Oncol. 2011 Nov 1. 29(31):4088-95. [QxMD MEDLINE Link].

37. Knauf WU, Lissitchkov T, Aldaoud A, Liberati AM, Loscertales J, Herbrecht R, et al. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol. 2012 Oct. 159(1):67-77. [QxMD MEDLINE Link].

38. Fischer K, Cramer P, Busch R, et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2011 Sep 10. 29(26):3559-66. [QxMD MEDLINE Link].

39. Castellino AM. 'Possibility of Cure' for Some Patients With CLL. Medscape Medical News. Available at https://www.medscape.com/viewarticle/918027. September 10, 2019; Accessed: January 12, 2023.

40. St-Pierre F, Ma S. Use of BTK Inhibitors in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): A Practical Guidance. Blood Lymphat Cancer. 2022. 12:81-98. [QxMD MEDLINE Link]. [Full Text].

41. Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013 Jul 4. 369(1):32-42. [QxMD MEDLINE Link]. [Full Text].

42. Chustecka Z. Ibrutinib in CLL: indication expanded, benefit confirmed. Medscape Medical News. Available at http://www.medscape.com/viewarticle/828980. July 28, 2014; Accessed: January 12, 2023.

43. Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014 Jul 17. 371 (3):213-23. [QxMD MEDLINE Link]. [Full Text].

44. Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med. 2015 Dec 17. 373 (25):2425-37. [QxMD MEDLINE Link].

45. Langerbeins P, Zhang C, Robrecht S et. al. The CLL12 trial: ibrutinib vs placebo in treatment-naïve, early-stage chronic lymphocytic leukemia. Blood. 2022 Jan 13. 139 (2):177-187. [QxMD MEDLINE Link].

46. Seymour JF. CLL12: a positive answer to a poorly phrased question. Blood. 2022 Jan 13. 139 (2):151-152. [QxMD MEDLINE Link].

47. Dickerson T, Wiczer T, Waller A, Philippon J, Porter K, Haddad D, et al. Hypertension and Incident Cardiovascular Events Following Ibrutinib Initiation. Blood. 2019 Oct 3. 118 (8):2062-8. [QxMD MEDLINE Link]. [Full Text].

48. Salem JE, Manouchehri A, Bretagne M, Lebrun-Vignes B, Groarke JD, Johnson DB, et al. Cardiovascular Toxicities Associated With Ibrutinib. J Am Coll Cardiol. 2019 Oct 1. 74 (13):1667-1678. [QxMD MEDLINE Link].

49. Burger JA. Treatment of Chronic Lymphocytic Leukemia. N Engl J Med. 2020 Jul 30. 383 (5):460-473. [QxMD MEDLINE Link]. [Full Text].

50. Puła B, Gołos A, Górniak P, Jamroziak K. Overcoming Ibrutinib Resistance in Chronic Lymphocytic Leukemia. Cancers (Basel). 2019 Nov 21. 11 (12):[QxMD MEDLINE Link]. [Full Text].

51. Hoang, T., Cheung, M., Chan, K., et al. The Impact of Drug Interactions on Outcomes in Ibrutinib-Treated Patients with Chronic Lymphocytic Leukemia in Routine Clinical Care: A Population-Based Cohort Study. American Society of Hematology. Available at https://ash.confex.com/ash/2022/webprogram/Paper158768.html. December 12, 2022; Accessed: January 12, 2023.

52. Project Orbis: FDA approves acalabrutinib for CLL and SLL. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/project-orbis-fda-approves-acalabrutinib-cll-and-sll. November 21, 2019; Accessed: January 12, 2023.

53. Sharman JP, Egyed M, Jurczak W, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naïve chronic lymphocytic leukemia. Leukemia. 2022 Jan 1. [QxMD MEDLINE Link]. [Full Text].

54. Byrd JC, Woyach JA, Furman RR, Martin P, O'Brien S, Brown JR, et al. Acalabrutinib in treatment-naive chronic lymphocytic leukemia. Blood. 2021 Jun 17. 137 (24):3327-3338. [QxMD MEDLINE Link].

55. Real-World Study Shows Patients Treated with IMBRUVICA® (ibrutinib) Were Less Likely to Initiate a Next-Line Treatment than Patients on Acalabrutinib in First-line Chronic Lymphocytic Leukemia. Johnson & Johnson. December 12, 2022. Available at https://www.jnj.com/real-world-study-shows-patients-treated-with-imbruvica-ibrutinib-were-less-likely-to-initiate-a-next-line-treatment-than-patients-on-acalabrutinib-in-first-line-chronic-lymphocytic-leukemia.

56. McKnight P. FDA Oks Zanubrutinib (Brukinsa) for CLL or SLL. Medscape Medical News. Available at https://www.medscape.com/viewarticle/987252. January 20, 2023; Accessed: January 27, 2023.

57. Brown JR, Eichhorst B, Hillmen P, Jurczak W, Kaźmierczak M, Lamanna N, et al. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2022 Dec 13. [QxMD MEDLINE Link].

58. Venclexta (venetoclax) [package insert]. North Chicago, IL: AbbVie, Inc. May 2019. Available at [Full Text].

59. FDA approves venetoclax for CLL and SLL. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-venetoclax-cll-and-sll. May 15, 2019; Accessed: September 13, 2019.

60. FDA approves venetoclax for CLL and SLL. U.S. Food Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-venetoclax-cll-and-sll. May 15, 2019; Accessed: November 7, 2022.

61. Seymour JF, Kipps TJ, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, et al. Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2018 Mar 22. 378 (12):1107-1120. [QxMD MEDLINE Link].

62. Kater AP, Seymour JF, Hillmen P, Eichhorst B, Langerak AW, Owen C, et al. Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study. J Clin Oncol. 2019 Feb 1. 37 (4):269-277. [QxMD MEDLINE Link]. [Full Text].

63. Jain N, Keating M, Thompson P, et al. Ibrutinib and Venetoclax for First-Line Treatment of CLL. N Engl J Med. 2019 May 30. 380 (22):2095-2103. [QxMD MEDLINE Link].

64. Kater AP, et al; GLOW Investigators. Fixed-Duration Ibrutinib-Venetoclax in Patients with Chronic Lymphocytic Leukemia and Comorbidities. N Engl J Med Evidence. May 13, 2022. 1(7):[Full Text].

65. Three-Drug Combination Therapy Effective in Patients with High-Risk CLL, Trial Shows. Dana-Farber Cancer Institute. December 10, 2022. Available at https://www.dana-farber.org/newsroom/news-releases/2022/three-drug-combination-therapy-effective-in-patients-with-high-risk-cll--trial-shows/.

66. Mato AR, Shah NN, Jurczak W, Cheah CY, Pagel JM, Woyach JA, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021 Mar 6. 397 (10277):892-901. [QxMD MEDLINE Link].

67. Awan FT, Hillmen P, Hellmann A, Robak T, Hughes SG, Trone D, et al. A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia. Br J Haematol. 2014 Nov. 167 (4):466-77. [QxMD MEDLINE Link].

68. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20. 370 (12):1101-10. [QxMD MEDLINE Link]. [Full Text].

69. McCall B. Obinutuzumab Active in Elderly Chronic Lymphocytic Leukemia. Medscape Medical News from the 18th Congress of the European Hematology Association (EHA). Available at http://www.medscape.com/viewarticle/806700. June 21, 2013; Accessed: January 12, 2023.

70. Moreno C, Greil R, Demirkan F, Tedeschi A, Anz B, Larratt L, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019 Jan. 20 (1):43-56. [QxMD MEDLINE Link].

71. Lemery SJ, Zhang J, Rothmann MD, Yang J, Earp J, Zhao H. U.S. Food and Drug Administration approval: ofatumumab for the treatment of patients with chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab. Clin Cancer Res. 2010 Sep 1. 16(17):4331-8. [QxMD MEDLINE Link].

72. Nelson R. FDA Grants Full Approval to Ofatumumab (Arzerra) for CLL. Medscape Medical News. Available at http://www.medscape.com/viewarticle/823837. April 17, 2014; Accessed: January 12, 2023.

73. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014 Mar 13. 370(11):997-1007. [QxMD MEDLINE Link]. [Full Text].

74. van Oers MH, Kuliczkowski K, Smolej L, Petrini M, Offner F, Grosicki S, et al. Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study. Lancet Oncol. 2015 Oct. 16 (13):1370-9. [QxMD MEDLINE Link].

75. Robak, T, Warzocha, K, Babu, KG, et al. Health-Related Quality of Life and Patient-Reported Outcomes in Patients Receiving Ofatumumab in Combination with Fludarabine and Cyclophosphamide (FC) Versus FC Alone in the Complement 2 Trial. Blood. 2015. 126(23):5288. [Full Text].

76. Novartis Withdraws Chronic Leukemia Drug Arzerra From Non-U.S. Markets. FDA News. Available at https://www.fdanews.com/articles/185419-novartis-withdraws-chronic-leukemia-drug-arzerra-from-non-us-markets. January 30, 2018; Accessed: January 12, 2023.

77. Nabhan C, Coutré S, Hillmen P. Minimal residual disease in chronic lymphocytic leukaemia: is it ready for primetime?. Br J Haematol. 2007 Feb. 136(3):379-92. [QxMD MEDLINE Link].

78. Sayala HA, Rawstron AC, Hillmen P. Minimal residual disease assessment in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol. 2007 Sep. 20(3):499-512. [QxMD MEDLINE Link].

79. Parikh SA, Keating MJ, O'Brien S, et al. Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia. Blood. 2011 Aug 25. 118(8):2062-8. [QxMD MEDLINE Link].

80. Badoux XC, Keating MJ, Wang X, et al. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia. Blood. 2011 Aug 25. 118(8):2085-93. [QxMD MEDLINE Link].

81. Skoetz N, Bauer K, Elter T, Monsef I, Roloff V, Hallek M, et al. Alemtuzumab for patients with chronic lymphocytic leukaemia. Cochrane Database Syst Rev. 2012 Feb 15. CD008078. [QxMD MEDLINE Link]. [Full Text].

82. Mougalian SS, O'Brien S. Adverse prognostic features in chronic lymphocytic leukemia. Oncology (Williston Park). 2011 Jul. 25(8):692-6, 699. [QxMD MEDLINE Link].

83. Woyach JA, Ruppert AS, Heerema NA, Peterson BL, Gribben JG, Morrison VA, et al. Chemoimmunotherapy With Fludarabine and Rituximab Produces Extended Overall Survival and Progression-Free Survival in Chronic Lymphocytic Leukemia: Long-Term Follow-Up of CALGB Study 9712. J Clin Oncol. 2011 Apr 1. 29(10):1349-55. [QxMD MEDLINE Link].

84. Robak T, Dmoszynska A, Solal-Celigny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010 Apr 1. 28(10):1756-65. [QxMD MEDLINE Link].

85. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010 Oct 2. 376(9747):1164-74. [QxMD MEDLINE Link].

86. Elter T, Gercheva-Kyuchukova L, Pylylpenko H, Robak T, Jaksic B, Rekhtman G, et al. Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a randomised phase 3 trial. Lancet Oncol. 2011 Dec. 12 (13):1204-13. [QxMD MEDLINE Link]. [Full Text].

87. Badoux XC, Keating MJ, Wang X, O'Brien SM, Ferrajoli A, Faderl S, et al. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia. Blood. 2011 Aug 25. 118 (8):2085-93. [QxMD MEDLINE Link]. [Full Text].

88. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20. 370 (12):1101-10. [QxMD MEDLINE Link]. [Full Text].

89. Chustecka Z. Idelalisib (Zydelig) approved for CLL and lymphoma. Medscape Medical News. July 23, 2014. [Full Text].

90. FDA news release: FDA approves Zydelig for three types of blood cancers. US Food and Drug Administration. July 23, 2014. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm.

91. Flinn IW, Hillmen P, Montillo M, Nagy Z, Illés Á, Etienne G, et al. The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood. 2018 Dec 6. 132 (23):2446-2455. [QxMD MEDLINE Link].

92. Gribben JG, Jurczak W, Jacobs RW, et al. Umbralisib Plus Ublituximab (U2) Is Superior to Obinutuzumab Plus Chlorambucil (O+Chl) in Patients with Treatment Naïve (TN) and Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Results from the Phase 3 Unity-CLL Study. Blood. November 5, 2020. 136 suppl 1:37-39. [Full Text].

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97. Gauthier J, Hirayama AV, Purushe J, Hay KA, Lymp J, Li DH, et al. Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure. Blood. 2020 May 7. 135 (19):1650-1660. [QxMD MEDLINE Link].

98. Melenhorst JJ, Chen GM, Wang M, et al. Decade-long leukaemia remissions with persistence of CD4⁺ CAR T cells. Nature. 2022 Feb 2. [QxMD MEDLINE Link]. [Full Text].

99. Eichhorst BF, Busch R, Stilgenbauer S, et al. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009 Oct 15. 114(16):3382-91. [QxMD MEDLINE Link].

100. Laurenti L, Innocenti I, Autore F, et al. Chlorambucil plus rituximab as front-line therapy for elderly and/or unfit chronic lymphocytic leukemia patients: correlation with biologically-based risk stratification. Haematologica. 2017 Sep. 102 (9):e352-e355. [QxMD MEDLINE Link]. [Full Text].

101. Woyach JA, Ruppert AS, Rai K, Lin TS, Geyer S, Kolitz J, et al. Impact of Age on Outcomes After Initial Therapy With Chemotherapy and Different Chemoimmunotherapy Regimens in Patients With Chronic Lymphocytic Leukemia: Results of Sequential Cancer and Leukemia Group B Studies. J Clin Oncol. 2012 Dec 10. [QxMD MEDLINE Link].

102. Gribben JG, Hosing C, Maloney DG. Stem cell transplantation for indolent lymphoma and chronic lymphocytic leukemia. Biol Blood Marrow Transplant. 2011 Jan. 17(1 Suppl):S63-70. [QxMD MEDLINE Link].

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Mohammad Muhsin Chisti, MD, FACP Associate Professor of Medicine (Hematology and Oncology), Oakland University William Beaumont School of Medicine; Medical Director of Research, Karmanos Cancer Institute

Mohammad Muhsin Chisti, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.

Bilal M Ali, BS MD Candidate, Oakland University William Beaumont School of Medicine

Disclosure: Nothing to disclose.

Emma L Herrman, MD Resident Physician, Department of Internal Medicine, Beaumont Hospital

Emma L Herrman, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians

Disclosure: Nothing to disclose.

Mariam Aoun, MD Resident Physician, Department of Internal Medicine, Beaumont Hospital – Royal Oak

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Haleem J Rasool, MD, FACP Chair, Department of Oncology, Mayo Clinic Health System, La Crosse, WI

Haleem J Rasool, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Delong Liu, MD, PhD Professor of Medicine, Division of Oncology/Hematology, New York Medical College; Chief of Hematology, Phelps Memorial Hospital Center; Director of Non-ablative Allogeneic Stem Cell Transplantation Program, Westchester Medical Center; Editor-in-Chief, Journal of Hematology and Oncology

Delong Liu, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Samir C Patel, MD Fellow, Department of Hematology and Medical Oncology, Metropolitan Hospital, New York Medical College

Disclosure: Nothing to disclose.

Muhammad A Mir, MD, FACP Assistant Professor of Medicine (Hematology, Blood/Marrow Transplant) Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Muhammad A Mir, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Michael Perry, MD, MS, MACP† Former Nellie B Smith Chair of Oncology Emeritus, Former Director, Division of Hematology and Medical Oncology, Former Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

Clarence Sarkodee-Adoo, MD Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Disclosure: Takeda Millenium Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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