Milena Kohn , Tamim Alsuliman , Sylvain Lamure , Morgane Cheminant, J eremy Delage, Corinne Merle De Boever, Jean Jacques Tudesq, Zora Marjanovic, Zo e Van de Wyngaert, Florent Malard, Eolia Brissot, Sophie Rigaudeau, St ephanie Marque-Juillet, Audrey Therby, Guillaume Cartron, Philippe Rousselot, Olivier Hermine, R emy Dul ery† and Caroline Besson† Service d’H ematologie, Centre Hospitalier de Versailles, Le Chesnay, France; Sorbonne Universit e, INSERM UMRs938, Service d’H ematologie Clinique et de Th erapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France; Department of Clinical Hematology, Montpellier University Hospital, IGMM UMR5535 CNRS, University of Montpellier, Montpellier, France; Service d’H ematologie, Hôpital Necker, Paris, France; Service d’H ematologie, Clinique du Parc, France; D epartement des maladies infectieuses et tropicales, Montpellier University Hospital, Montpellier, France; Laboratoire de virologie, Centre Hospitalier de Versailles, Le Chesnay, France; Service de m edecine interne, Centre Hospitalier de Versailles, Le Chesnay, France; UVSQ, Inserm, Equipe "Exposome et H er edit e", CESP, Universit e Paris-Saclay, Villejuif, France

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Characteristics of SARS-CoV-2 infection in lymphoma/chronic lymphocytic leukemia patients during the Omicron outbreak

COVID‐19, the disease caused by SARS‐CoV‐2, is still afflicting thousands of people across the globe. Few studies on COVID‐19 in chronic lymphocytic leukemia (CLL) are available. Here, we analyzed data from the CLL cohort of the Italian Hematology Alliance on COVID‐19 (NCT04352556), which included 256 CLL patients enrolled between 25 February 2020 and 1 February 2021. Median age was 70 years (range 38–94) with male preponderance (60.1%). Approximately half of patients (n = 127) had received at least one line of therapy for CLL, including 108 (83.7%) who were on active treatment at the time of COVID‐19 or received their last therapy within 12 months. Most patients (230/256, 89.9%) were symptomatic at COVID‐19 diagnosis and the majority required hospitalization (n = 176). Overall, after a median follow‐up of 42 days (IQR 24–96), case fatality rate was 30.1%, and it was 37.5% and 24.4% in the first (25 February 2020–22 June 2020) and second wave (23 June 2020–1 February 2021), respectively (p = 0.03). At multivariate analysis, male sex (HR 1.82, 95% CI 1.03–3.24, p = 0.04), age over than 70 years (HR 2.23, 95% CI 1.23–4.05, p = 0.01), any treatment for CLL given in the last 12 months (HR 1.72, 95% CI 1.04–2.84, p = 0.04) and COVID‐19 severity (severe: HR 5.66, 95% CI 2.62–12.33, p < 0.0001; critical: HR 15.99, 95% CI 6.93–36.90, p < 0.0001) were independently associated with poor survival. In summary, we report a dismal COVID‐related outcome in a significant fraction of CLL patients, that can be nicely predicted by clinical parameters.

SARS‐CoV‐2 infection in patients with chronic lymphocytic leukemia: The Italian Hematology Alliance on COVID‐19 cohort

Abstract Patients with haematological malignancies (HM) and SARS-CoV-2 infection present a higher risk of severe COVID-19 and mortality. The aim of the study was to investigate whether vaccination and monoclonal antibodies (mAbs) have modified the outcomes of HM patients with COVID-19. This is a single-centre retrospective study in HM patients hospitalized due to SARS-CoV-2 infection from March 2020 to April 2022. Patients were divided into PRE-V-mAb group (patients hospitalized before the introduction of vaccination and mAbs) and POST-V-mAb group (patients hospitalized after the use of vaccine and mAbs). A total of 126 patients were included (65 PRE-V-mAb and 61 POST-V-mAb). POST-V-mAb patients showed a significantly lower risk of intensive care unit (ICU) admission (8.2% vs. 27.7%, p = 0.005), shorter viral shedding [17 (IQR 10–28) vs. 24 days (IQR 15–50), p = 0.011] and shorter hospitalization length [13 (IQR 7–23) vs. 20 (IQR 14–41) days, p = 0.0003] compared to the PRE-V-mAb group. Nevertheless, both in-hospital and 30-day mortality rates did not significantly differ between the two groups (29.5% POST-V-mAb vs. 36.9% PRE-V-mAb and 21.3% POST-V-mAb vs. 29.2% PRE-V-mAb, respectively). At the multivariable analysis, an active malignancy ( p = 0.042), a critical COVID-19 at admission ( p = 0.025) and the need for high-level of oxygen support at respiratory worsening [either HFNC/CPAP ( p = 0.022) or mechanical ventilation ( p = 0.011)] were independently associated with in-hospital mortality. In the subgroup of POST-V-mAb patients, receiving therapy with mAbs was a protective factor ( p = 0.033). Despite the new therapeutic and preventive strategies available, HM patients with COVID-19 disease represent an extremely vulnerable group with still high mortality rates. 

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Outcome of COVID-19 patients with haematological malignancies after the introduction of vaccination and monoclonal antibodies: results from the HM-COV 2.0 study

Simple Summary We prospectively analyzed COVID-19 morbidity and severity in 200 consecutive patients with CLL. Increased COVID-19 morbidity was observed in vaccinated patients with CLL. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19. Most patients, 36.5%, experienced COVID-19 during the Omicron pandemic, 26% of patients were hospitalized, and 4% died. Moreover, 10% had re-infections. In multivariate analysis of elderly patients, TP53 disrupted, heavily pre-treated, and those in early treatment with targeted agents showed increased vulnerability to COVID-19. Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in patients with CLL. Abstract High morbidity and mortality due to COVID-19 were described in the pre-vaccination era in patients with chronic lymphocytic leukemia (CLL). To evaluate COVID-19 morbidity after the SARS-CoV-2 vaccine, we carried out a prospective study in 200 CLL patients. The median age of patients was 70 years; 35% showed IgG levels ≤ 550 mg/dL, 61% unmutated IGHV, and 34% showed TP53 disruption. Most patients, 83.5%, were previously treated, including 36% with ibrutinib and 37.5% with venetoclax. The serologic response rates to the second and third dose of the vaccine were 39% and 53%, respectively. With a median follow-up of 23.4 months, 41% of patients experienced COVID-19, 36.5% during the Omicron pandemic, and 10% had subsequent COVID-19 events. Severe COVID-19 requiring hospitalization was recorded in 26% of patients, and 4% died. Significant and independent factors associated with the response to the vaccine and vulnerability to COVID-19 were age (OR: 0.93; HR: 0.97) and less than 18 months between the start of targeted agents and vaccine (OR: 0.17; HR: 0.31). TP53 mutation and ≥two prior treatments also emerged as significant and independent factors associated with an increased risk of developing COVID-19 (HR: 1.85; HR: 2.08). No statistical difference in COVID-19 morbidity was found in patients with or without antibody response to the vaccine (47.5% vs. 52.5%; p = 0.21). Given the persistent risk of infection due to the continuous emergence of SARS-CoV-2 variants, our results support the importance of new vaccines and protective measures to prevent and mitigate COVID-19 in CLL patients.

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Antibody Response to the SARS-CoV-2 Vaccine and COVID-19 Vulnerability during the Omicron Pandemic in Patients with CLL: Two-Year Follow-Up of a Multicenter Study

Abstract Purpose . Patients with hematological malignancies (HM) and SARS-CoV-2 infection present a higher risk of severe COVID-19 and mortality. The aim of the study was to investigate whether vaccination and monoclonal antibodies (mAbs) have modified the outcomes of HM patients with COVID-19. Methods . Single-center retrospective study in HM patients hospitalized due to SARS-CoV-2 infection from March 2020 to April 2022. Patients were divided into PRE-V-mAb group (patients hospitalized before the introduction of vaccination and mAbs) and POST-V-mAb group (patients hospitalized after the use of vaccine and mAbs). Results . A total of 126 patients were included (65 PRE-V-mAb and 61 POST-V-mAb). POST-V-mAb patients showed a significantly lower risk of Intensive Care Unit (ICU) admission (8.2% vs 27.7%, p=0.005), shorter viral shedding [17 (IQR 10-28) vs 24 days (IQR 15-50), p=0.011] and shorter hospitalization length [13 (IQR 7-23) vs 20 (IQR 14-41) days, p=0.0003] compared to the PRE-V-mAb group. Nevertheless, both in-hospital and 30-day mortality rates did not significantly differ between the two groups (29.5% POST-V-mAb vs 36.9% PRE-V-mAb and 21.3% POST-V-mAb vs 29.2% PRE-V-mAb, respectively). At the multivariable analysis an active malignancy (p=0.042), a critical COVID-19 at admission (p=0.025) and the need for high-level of oxygen support at respiratory worsening [either HFNC/CPAP (p=0.022) or Mechanical Ventilation (p=0.011)] were independently associated with in-hospital mortality. In the subgroup of POST-V-mAb patients, receiving therapy with mAbs was a protective factor (p=0.033). Conclusion . Despite the new therapeutic and preventive strategies available, HM patients with COVID-19 disease represent an extremely vulnerable group with still high mortality rates. 

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http://www.cell.com/article/S1535610822001775/pdf

Mor Levi

Papers

COVID-19 in patients with lymphoproliferative diseases during the Omicron variant surge

"Real-Life" Data of Zanubrutinib in Patients with Waldenström Macroglobulinemia - a Multi-Center Retrospective Study