Outcomes of COVID-19 in patients with CLL: a multicenter international experience

Author:

Mato Anthony R.1,Roeker Lindsey E.1,Lamanna Nicole2,Allan John N.3ORCID,Leslie Lori4,Pagel John M.5,Patel Krish5,Osterborg Anders6,Wojenski Daniel7,Kamdar Manali8,Huntington Scott F.9ORCID,Davids Matthew S.10,Brown Jennifer R.10,Antic Darko11,Jacobs Ryan12,Ahn Inhye E.13,Pu Jeffrey14ORCID,Isaac Krista M.15ORCID,Barr Paul M.16ORCID,Ujjani Chaitra S.17,Geyer Mark B.1ORCID,Berman Ellin1,Zelenetz Andrew D.1ORCID,Malakhov Nikita3,Furman Richard R.3,Koropsak Michael4,Bailey Neil5ORCID,Hanson Lotta6,Perini Guilherme F.18,Ma Shuo7,Ryan Christine E.10,Wiestner Adrian13,Portell Craig A.15,Shadman Mazyar17,Chong Elise A.19,Brander Danielle M.20,Sundaram Suchitra21ORCID,Seddon Amanda N.22,Seymour Erlene23,Patel Meera23,Martinez-Calle Nicolas24ORCID,Munir Talha25,Walewska Renata26,Broom Angus27,Walter Harriet28ORCID,El-Sharkawi Dima29ORCID,Parry Helen30ORCID,Wilson Matthew R.31ORCID,Patten Piers E. M.32,Hernández-Rivas José-Ángel33ORCID,Miras Fatima34ORCID,Fernández Escalada Noemi35,Ghione Paola1ORCID,Nabhan Chadi36,Lebowitz Sonia1,Bhavsar Erica3,López-Jiménez Javier37ORCID,Naya Daniel38,Garcia-Marco Jose Antonio39ORCID,Skånland Sigrid S.40,Cordoba Raul41,Eyre Toby A.42ORCID

Affiliation:

1. Memorial Sloan-Kettering Cancer Center, New York, NY;

2. Columbia University Medical Center, New York, NY;

3. New York-Presbyterian Hospital, Weill Cornell Medicine, New York, NY;

4. John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ;

5. Swedish Cancer Institute, Seattle, WA;

6. Karolinska Institute, Solna, Sweden;

7. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL;

8. University of Colorado Cancer Center, Aurora, CO;

9. Division of Hematology and Oncology, Department of Internal Medicine, Yale University, New Haven, CT;

10. Dana-Farber Cancer Institute, Boston, MA;

11. Clinical Center Serbia, University of Belgrade, Belgrade, Serbia;

12. Levine Cancer Institute/Atrium Health, Charlotte, NC;

13. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;

14. Upstate Cancer Center, Syracuse, NY;

15. Emily Couric Clinical Cancer Center, Charlottesville, VA;

16. University of Rochester Wilmot Cancer Institute, Rochester, NY;

17. Fred Hutchinson Cancer Research Center, Seattle, WA;

18. Hospital Israelita Albert Einstein, São Paulo, Brazil;

19. University of Pennsylvania Abramson Cancer Center, Philadelphia, PA;

20. Division of Hematology and Oncology, Department of Internal Medicine, Duke University School of Medicine, Durham, NC;

21. Roswell Park Comprehensive Cancer Center, Buffalo, NY;

22. Rush University Medical Center, Chicago, IL;

23. Karmanos Cancer Institute, Wayne State University, Detroit, MI;

24. Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom;

25. St James's University Hospital, Leeds, United Kingdom;

26. Royal Bournemouth Hospital, Bournemouth, United Kingdom;

27. Western General Hospital, Edinburgh, United Kingdom;

28. Leicester Royal Infirmary, Leicester, United Kingdom;

29. The Royal Marsden Hospital, London, United Kingdom;

30. Division of Hematology and Oncology, Department of Internal Medicine, University of Birmingham, Birmingham, United Kingdom;

31. Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom;

32. Comprehensive Cancer Centre, King’s College, London, United Kingdom;

33. Hospital Universitario Infanta Leonor, Madrid, Spain;

34. University Hospital Doce de Octubre, Madrid, Spain;

35. Marques de Valdecilla University Hospital, Santander, Spain;

36. Caris Life Sciences, Irving, TX;

37. University Hospital Ramon y Cajal, Madrid, Spain;

38. University Hospital Infanta Elena, Valdemoro, Madrid, Spain;

39. Puerta de Hierra-Majadahonda University Hospital, Madrid, Spain;

40. Department of Cancer Immunology, Institute for Cancer Research, Oslo University, Oslo, Norway;

41. Fundacion Jimenez Diaz University Hospital, Madrid, Spain; and

42. Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom

Abstract

Abstract Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n = 198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median Cumulative Illness Rating Scale score was 8 (range, 4-32). Thirty-nine percent were treatment naive (“watch and wait”), while 61% had received ≥1 CLL-directed therapy (median, 2; range, 1-8). Ninety patients (45%) were receiving active CLL therapy at COVID-19 diagnosis, most commonly Bruton tyrosine kinase inhibitors (BTKi’s; n = 68/90 [76%]). At a median follow-up of 16 days, the overall case fatality rate was 33%, though 25% remain admitted. Watch-and-wait and treated cohorts had similar rates of admission (89% vs 90%), intensive care unit admission (35% vs 36%), intubation (33% vs 25%), and mortality (37% vs 32%). CLL-directed treatment with BTKi’s at COVID-19 diagnosis did not impact survival (case fatality rate, 34% vs 35%), though the BTKi was held during the COVID-19 course for most patients. These data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death. Future epidemiologic studies are needed to assess severe acute respiratory syndrome coronavirus 2 infection risk, these data should be validated independently, and randomized studies of BTKi’s in COVID-19 are needed to provide definitive evidence of benefit.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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