Worldwide Examination of Patients with CLL Hospitalized for COVID-19

Roeker, Lindsey E.; Scarfò, Lydia; Chatzikonstantinou, Thomas; Abrisqueta, Pau; Eyre, Toby A.; Córdoba, Raúl; Prat, Ana Muntañola; Villacampa, Guillermo; Leslie, Lori A.; Koropsak, Michael; Quaresmini, Giulia; Allan, John N.; Furman, Richard R.; Bhavsar, Erica B.; Pagel, John M.; Hernández‐Rivas, José Ángel; Patel, Krish; Motta, Marina; Bailey, Neil; Mirás, Fatima; Lamanna, Nicole; Alonso, R.; Osorio-Prendes, Santiago; Vitale, Candida; Kamdar, Manali; Baltasar, Patricia; Österborg, Anders; Hanson, Lotta; Baile, Mónica; Rodríguez-Hernández, Inés; Valenciano, Susana; Popov, Viola Maria; Garcia, Abelardo Barez; Alfayate, A.; Oliveira, Ana Carla; Eichhorst, Barbara; Quaglia, Francesca Maria; Reda, Gianluigi; Jiménez, Javier López; Varettoni, Marzia; Marchetti, Monia; Romero, Pilar; Grau, Rosalía Riaza; Munir, Talha; Zabalza, Amaya; Janssens, Ann; Niemann, Carsten Utoft; Perini, Guilherme Fleury; Delgado, Julio; Segundo, Lucrecia Yáñez San; Roncero, Ma Isabel Gómez; Wilson, Matthew R.; Patten, Piers; Marasca, Roberto; Iyengar, Sunil; Seddon, Amanda N.; Torres, Ana; Ferrari, Ângela; Cuéllar-García, Carolina; Wojenski, Daniel; El‐Sharkawi, Dima; Itchaki, Gilad; Parry, Helen; Mateos-Mazón, Juan J.; Martínez‐Calle, Nicolás; Ma, Shuo; Naya, Daniel E.; Spek, Ellen van der; Seymour, Erlene; Vázquez, Eva Gimeno; Rigolin, Gian Matteo; Mauro, Francesca Romana; Walter, Harriet S.; Labrador, Jorge; Paoli, Lorenzo De; Laurenti, Luca; Ruíz, Elena; Levin, Mark‐David; Šimkovič, Martin; Špaček, Martin; Andreu, Rafa; Walewska, Renata; Pérez-González, Sonia; Sundaram, Suchitra; Wiestner, Adrian; Cuesta, Amalia; Broom, Angus; Kater, Arnon P.; Muiña, Begoña; Velasquez, César A; Ujjani, Chaitra S.; Serí, Cristina; Antić, Darko; Bron, Dominique; Vandenberghe, Elisabeth; Chong, Elise A.; Lista, Enrico; García, Fiz Campoy; Poeta, Giovanni Del; Ahn, Inhye E.; Pu, Jeffrey J.; Brown, Jennifer R.; Campos, Juan Alfonso Soler; Malerba, Lara; Trentin, Livio; Orsucci, Lorella; Farina, Lucia; Villalón, Lucı́a; Vidal, María; Sánchez, María José Ramirez; Terol, María José; Paolis, Maria Rosaria De; Gentile, Massimo; Davids, Matthew S.; Shadman, Mazyar; Yassin, Mohamed A; Foglietta, Myriam; Jakšić, Ozren; Sportoletti, Paolo; Barr, Paul M.; Ramos, Rafael; Santiago, Raquel; Ruchlemer, Rosa; Kersting, Sabina; Huntington, Scott F.; Herold, Tobias; Herishanu, Yair; Thompson, Meghan C.; Lebowitz, Sonia; Ryan, Christine E.; Jacobs, Ryan; Portell, Craig A.; Isaac, Krista; Rambaldi, Alessandro; Nabhan, Chadi; Brander, Danielle M.; Montserrat, Emili; Rossi, Giuseppe; García-Marco, José A.; Coscia, Marta; Malakhov, Nikita; Fernandez-Escalada, Noemi; Skånland, Sigrid S.; Coombs, Callie C.; Ghione, Paola; Schuster, Stephen J.; Foà, Robin; Cuneo, Antonio; Bosch, Francesc; Σταματόπουλος, Κώστας; Ghia, Paolo; Mato, Anthony R.; Patel, Meera

doi:10.1182/blood-2020-136408

Cited by 3 publications

(4 citation statements)

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“…The CFR in the entire cohort was 27.4% and increased to 38.4% among patients with severe COVID-19. This indicates a remarkable consistency among different studies in patients with CLL and COVID-19 as well as in the different waves of the pandemic, confirming the unabated aggressiveness of the disease with time [ 14 – 16 ]. In the general population, the CFR in hospitalized patients appears lower compared to our cohort: indicatively, a meta-analysis of COVID-19 patients found a fatality rate of 17.1% and 40.5% for hospitalized and critically ill patients, respectively [ 27 ].…”

Section: Discussionmentioning

confidence: 67%

“…In this updated cohort, patients treated for CLL had a worse OS than untreated patients, while in both the report by Mato et al (198 patients, end point: outcome) and our previous report (190 patients, end point: severity), no difference was found between treated and untreated patients, probably due to the lower number of cases [ 14 , 15 ]. Of note, when our previous cohort was combined with the Spanish cohort (281 patients), untreated patients had better OS than treated ones [ 16 ]. Thus, these apparent discrepancies may simply reflect the larger sample of our current analysis that allowed to identify a difference between the untreated and the treated, likely more immunosuppressed, patients.…”

Section: Discussionmentioning

confidence: 99%

“…Age was the only risk factor of fatality in both cohorts, while the effect of CLL treatment on OS was inconsistent across cohorts. None of the CLL-directed treatments affected OS [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

et al. 2021

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Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

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COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

et al. 2021

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“…The recommendations in this regard primarily reflect the first wave of the outbreak and include editorials, opinions, letters to the editor, commentaries, and conference proceedings [73][74]. Furthermore, the majority of the data used to develop these recommendations came from patients who were on BTKi therapy at the time of COVID19 infection, whereas information obtained from patients receiving venetoclax-based therapy at the time of COVID19 infection are limited [71][72]75]. Since our understanding of the COVID-19 pandemic is constantly evolving updated and more comprehensive recommendations are awaited.…”

Section: Expert Opinionsmentioning

confidence: 99%

Current and emerging investigational venetoclax-based therapies in chronic lymphocytic leukemia

Molica

Allsup

Gianfelici

et al. 2021

Expert Opinion on Investigational Drugs

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Introduction: Venetoclax has emerged as a breakthrough treatment which revolutionized the therapeutic paradigm of chronic lymphocytic leukemia (CLL). This is primarily due to the efficacy of venetoclax as time-limited, chemo-free, therapy in a therapeutic area dominated by targeted agents given on a continuous schedule. Furthermore, compelling clinical data support the use of venetoclax in combination with other targeted agents in the hope of preventing drug resistance due to the emergence of acquired mutations. Areas covered:This review provides an overview on clinical results of newly approved or under clinical development venetoclax-based therapies for CLL. In view of current and potential roles in CLL care, the strengths and disadvantages of venetoclax-combinations are discussed. The MEDLINE database, ClinicalTrials.gov and conference proceedings were all reviewed to select the relevant literature.Expert Opinion: While the advent of venetoclax-based combinations has significantly expanded the therapeutic options for patients with CLL, further research with longer follow-up is required to address remaining open questions such as (I) the role of venetoclax in driving the duration of therapy, (II) timing and threshold of minimal residual disease (MRD) assessment for stopping therapy, (III) the efficacy of novel triplet combinations using venetoclax as backbone, (IV) indications for re-initiating therapy with venetoclax. Article highlights-Targeting the bcl-2 pathway is a rational treatment approach in CLL. Therefore addition of venetoclax to the toolkit of CLL therapy represents important progress in the field.-Double or triple, chemo-free, venetoclax-based combinations have been recently evaluated in CLL. The idea behind this regimens is to administer therapy for a defined period, rather than exposing patients to endless treatment.-With the widespread use of venetoclax-based regimens, treatment of CLL patients who become refractory to novel agents is an area of unmet need.-Future directions to overcome resistance mechanisms to venetoclax should explore new approach based on novel BH3 mimetic developed to interact with either MCL-1 protein or transcriptional regulator of Mcl-1 expression.-Cellular therapies (i.e., CAR-T) are challenging in patients with progressive disease who are double-refractory.

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Managing the Risk of Infection in Chronic Lymphocytic Leukemia in the Era of New Therapies

Rivera

Ferrajoli

2022

Curr Oncol Rep

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Purpose of Review Patients diagnosed with CLL have an increased susceptibility to infections. Over the years, there has been a shift of the treatment arsenal to an increasing use of chemotherapy-free regimens, particularly small molecule inhibitors. These therapies have proven to be effective and have a favorable toxicity profile. Infections continue to represent a significant complication in the era of novel therapies. Recent Findings Recent studies continue to bring new insights into the effects of modern therapies on the immune system. Evidence supporting infection prevention strategies is scarce. We will review the available recommendations to prevent infections in patients with CLL treated with novel therapies. Summary New CLL therapies are broadly adopted in routine practice, requiring optimization of their side effects. Timely prevention, recognition, and treatment of infections should remain an important aspect of the standard management of a patient with CLL.

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Worldwide Examination of Patients with CLL Hospitalized for COVID-19

Cited by 3 publications

References 0 publications

COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Current and emerging investigational venetoclax-based therapies in chronic lymphocytic leukemia

Managing the Risk of Infection in Chronic Lymphocytic Leukemia in the Era of New Therapies

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