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

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

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.