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

Anthony R. Mato; Lindsey E. Roeker; Nicole Lamanna; John N. Allan; Lori Leslie; John M. Pagel; Krish Patel; Anders Osterborg; Daniel Wojenski; Manali Kamdar; Scott F. Huntington; Matthew S. Davids; Jennifer R. Brown; Darko Antic; Ryan Jacobs; Inhye E. Ahn; Jeffrey Pu; Krista M. Isaac; Paul M. Barr; Chaitra S. Ujjani; Mark B. Geyer; Ellin Berman; Andrew D. Zelenetz; Nikita Malakhov; Richard R. Furman; Michael Koropsak; Neil Bailey; Lotta Hanson; Guilherme F. Perini; Shuo Ma; Christine E. Ryan; Adrian Wiestner; Craig A. Portell; Mazyar Shadman; Elise A. Chong; Danielle M. Brander; Suchitra Sundaram; Amanda N. Seddon; Erlene Seymour; Meera Patel; Nicolas Martinez-calle; Talha Munir; Renata Walewska; Angus Broom; Harriet Walter; Dima El-sharkawi; Helen Parry; Matthew R. Wilson; Piers E. M. Patten; José-ángel Hernández-rivas; Fatima Miras; Noemi Fernández Escalada; Paola Ghione; Chadi Nabhan; Sonia Lebowitz; Erica Bhavsar; Javier López-Jiménez; Daniel Naya; Jose Antonio Garcia-marco; Sigrid S. Skånland; Raul Cordoba; Toby A. Eyre

doi:10.1182/blood.2020006965

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

Anthony R. Mato, Lindsey E. Roeker, Nicole Lamanna, John N. Allan, Lori Leslie, John M. Pagel, Krish Patel, Anders Osterborg, Daniel Wojenski, Manali Kamdar, Scott F. Huntington, Matthew S. Davids, Jennifer R. Brown, Darko Antic, Ryan Jacobs, Inhye E. Ahn, Jeffrey Pu, Krista M. Isaac, Paul M. Barr, Chaitra S. UjjaniMark B. Geyer, Ellin Berman, Andrew D. Zelenetz, Nikita Malakhov, Richard R. Furman, Michael Koropsak, Neil Bailey, Lotta Hanson, Guilherme F. Perini, Shuo Ma, Christine E. Ryan, Adrian Wiestner, Craig A. Portell, Mazyar Shadman, Elise A. Chong, Danielle M. Brander, Suchitra Sundaram, Amanda N. Seddon, Erlene Seymour, Meera Patel, Nicolas Martinez-calle, Talha Munir, Renata Walewska, Angus Broom, Harriet Walter, Dima El-sharkawi, Helen Parry, Matthew R. Wilson, Piers E. M. Patten, José-ángel Hernández-rivas, Fatima Miras, Noemi Fernández Escalada, Paola Ghione, Chadi Nabhan, Sonia Lebowitz, Erica Bhavsar, Javier López-Jiménez, Daniel Naya, Jose Antonio Garcia-marco, Sigrid S. Skånland, Raul Cordoba, Toby A. Eyre

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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.

Original language	English
Pages (from-to)	1134-1143
Number of pages	8
Journal	Blood
Volume	136
Issue number	10
Early online date	20 Jul 2020
DOIs	https://doi.org/10.1182/blood.2020006965
Publication status	Published - 3 Sept 2020

Keywords

Adult
Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors
Aged
Aged, 80 and over
Anti-Inflammatory Agents/therapeutic use
Antiviral Agents/therapeutic use
Betacoronavirus/isolation & purification
COVID-19
Coronavirus Infections/complications
Female
Humans
Immunization, Passive
Leukemia, Lymphocytic, Chronic, B-Cell/complications
Male
Middle Aged
Pandemics
Pneumonia, Viral/complications
Protein Kinase Inhibitors/therapeutic use
SARS-CoV-2
Survival Analysis
Treatment Outcome

ASJC Scopus subject areas

Hematology
Biochemistry
Cell Biology
Immunology

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Cite this

Mato, A. R., Roeker, L. E., Lamanna, N., Allan, J. N., Leslie, L., Pagel, J. M., Patel, K., Osterborg, A., Wojenski, D., Kamdar, M., Huntington, S. F., Davids, M. S., Brown, J. R., Antic, D., Jacobs, R., Ahn, I. E., Pu, J., Isaac, K. M., Barr, P. M., ... Eyre, T. A. (2020). Outcomes of COVID-19 in patients with CLL: a multicenter international experience. Blood, 136(10), 1134-1143. https://doi.org/10.1182/blood.2020006965

@article{627886e93d594092903a8d253cf5e482,

title = "Outcomes of COVID-19 in patients with CLL: a multicenter international experience",

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{\textquoteright}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{\textquoteright}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{\textquoteright}s in COVID-19 are needed to provide definitive evidence of benefit.",

keywords = "Adult, Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors, Aged, Aged, 80 and over, Anti-Inflammatory Agents/therapeutic use, Antiviral Agents/therapeutic use, Betacoronavirus/isolation & purification, COVID-19, Coronavirus Infections/complications, Female, Humans, Immunization, Passive, Leukemia, Lymphocytic, Chronic, B-Cell/complications, Male, Middle Aged, Pandemics, Pneumonia, Viral/complications, Protein Kinase Inhibitors/therapeutic use, SARS-CoV-2, Survival Analysis, Treatment Outcome",

author = "Mato, {Anthony R.} and Roeker, {Lindsey E.} and Nicole Lamanna and Allan, {John N.} and Lori Leslie and Pagel, {John M.} and Krish Patel and Anders Osterborg and Daniel Wojenski and Manali Kamdar and Huntington, {Scott F.} and Davids, {Matthew S.} and Brown, {Jennifer R.} and Darko Antic and Ryan Jacobs and Ahn, {Inhye E.} and Jeffrey Pu and Isaac, {Krista M.} and Barr, {Paul M.} and Ujjani, {Chaitra S.} and Geyer, {Mark B.} and Ellin Berman and Zelenetz, {Andrew D.} and Nikita Malakhov and Furman, {Richard R.} and Michael Koropsak and Neil Bailey and Lotta Hanson and Perini, {Guilherme F.} and Shuo Ma and Ryan, {Christine E.} and Adrian Wiestner and Portell, {Craig A.} and Mazyar Shadman and Chong, {Elise A.} and Brander, {Danielle M.} and Suchitra Sundaram and Seddon, {Amanda N.} and Erlene Seymour and Meera Patel and Nicolas Martinez-calle and Talha Munir and Renata Walewska and Angus Broom and Harriet Walter and Dima El-sharkawi and Helen Parry and Wilson, {Matthew R.} and Patten, {Piers E. M.} and Jos{\'e}-{\'a}ngel Hern{\'a}ndez-rivas and Fatima Miras and {Fern{\'a}ndez Escalada}, Noemi and Paola Ghione and Chadi Nabhan and Sonia Lebowitz and Erica Bhavsar and Javier L{\'o}pez-Jim{\'e}nez and Daniel Naya and Garcia-marco, {Jose Antonio} and Sk{\aa}nland, {Sigrid S.} and Raul Cordoba and Eyre, {Toby A.}",

year = "2020",

month = sep,

day = "3",

doi = "10.1182/blood.2020006965",

language = "English",

volume = "136",

pages = "1134--1143",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "10",

}

Mato, AR, Roeker, LE, Lamanna, N, Allan, JN, Leslie, L, Pagel, JM, Patel, K, Osterborg, A, Wojenski, D, Kamdar, M, Huntington, SF, Davids, MS, Brown, JR, Antic, D, Jacobs, R, Ahn, IE, Pu, J, Isaac, KM, Barr, PM, Ujjani, CS, Geyer, MB, Berman, E, Zelenetz, AD, Malakhov, N, Furman, RR, Koropsak, M, Bailey, N, Hanson, L, Perini, GF, Ma, S, Ryan, CE, Wiestner, A, Portell, CA, Shadman, M, Chong, EA, Brander, DM, Sundaram, S, Seddon, AN, Seymour, E, Patel, M, Martinez-calle, N, Munir, T, Walewska, R, Broom, A, Walter, H, El-sharkawi, D, Parry, H, Wilson, MR, Patten, PEM, Hernández-rivas, J, Miras, F, Fernández Escalada, N, Ghione, P, Nabhan, C, Lebowitz, S, Bhavsar, E, López-Jiménez, J, Naya, D, Garcia-marco, JA, Skånland, SS, Cordoba, R & Eyre, TA 2020, 'Outcomes of COVID-19 in patients with CLL: a multicenter international experience', Blood, vol. 136, no. 10, pp. 1134-1143. https://doi.org/10.1182/blood.2020006965

TY - JOUR

T1 - Outcomes of COVID-19 in patients with CLL

T2 - a multicenter international experience

AU - Mato, Anthony R.

AU - Roeker, Lindsey E.

AU - Lamanna, Nicole

AU - Allan, John N.

AU - Leslie, Lori

AU - Pagel, John M.

AU - Patel, Krish

AU - Osterborg, Anders

AU - Wojenski, Daniel

AU - Kamdar, Manali

AU - Huntington, Scott F.

AU - Davids, Matthew S.

AU - Brown, Jennifer R.

AU - Antic, Darko

AU - Jacobs, Ryan

AU - Ahn, Inhye E.

AU - Pu, Jeffrey

AU - Isaac, Krista M.

AU - Barr, Paul M.

AU - Ujjani, Chaitra S.

AU - Geyer, Mark B.

AU - Berman, Ellin

AU - Zelenetz, Andrew D.

AU - Malakhov, Nikita

AU - Furman, Richard R.

AU - Koropsak, Michael

AU - Bailey, Neil

AU - Hanson, Lotta

AU - Perini, Guilherme F.

AU - Ma, Shuo

AU - Ryan, Christine E.

AU - Wiestner, Adrian

AU - Portell, Craig A.

AU - Shadman, Mazyar

AU - Chong, Elise A.

AU - Brander, Danielle M.

AU - Sundaram, Suchitra

AU - Seddon, Amanda N.

AU - Seymour, Erlene

AU - Patel, Meera

AU - Martinez-calle, Nicolas

AU - Munir, Talha

AU - Walewska, Renata

AU - Broom, Angus

AU - Walter, Harriet

AU - El-sharkawi, Dima

AU - Parry, Helen

AU - Wilson, Matthew R.

AU - Patten, Piers E. M.

AU - Hernández-rivas, José-ángel

AU - Miras, Fatima

AU - Fernández Escalada, Noemi

AU - Ghione, Paola

AU - Nabhan, Chadi

AU - Lebowitz, Sonia

AU - Bhavsar, Erica

AU - López-Jiménez, Javier

AU - Naya, Daniel

AU - Garcia-marco, Jose Antonio

AU - Skånland, Sigrid S.

AU - Cordoba, Raul

AU - Eyre, Toby A.

PY - 2020/9/3

Y1 - 2020/9/3

N2 - 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.

AB - 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.

KW - Adult

KW - Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors

KW - Aged

KW - Aged, 80 and over

KW - Anti-Inflammatory Agents/therapeutic use

KW - Antiviral Agents/therapeutic use

KW - Betacoronavirus/isolation & purification

KW - COVID-19

KW - Coronavirus Infections/complications

KW - Female

KW - Humans

KW - Immunization, Passive

KW - Leukemia, Lymphocytic, Chronic, B-Cell/complications

KW - Male

KW - Middle Aged

KW - Pandemics

KW - Pneumonia, Viral/complications

KW - Protein Kinase Inhibitors/therapeutic use

KW - SARS-CoV-2

KW - Survival Analysis

KW - Treatment Outcome

UR - http://www.scopus.com/inward/record.url?scp=85089864394&partnerID=8YFLogxK

UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472711/

UR - https://europepmc.org/article/med/32688395

U2 - 10.1182/blood.2020006965

DO - 10.1182/blood.2020006965

M3 - Article

C2 - 32688395

SN - 0006-4971

VL - 136

SP - 1134

EP - 1143

JO - Blood

JF - Blood

IS - 10

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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