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745 Outcomes of Adult and Pediatric Patients with Hematologic Malignancies and COVID-19: A Systematic Review and Meta-Analysis of 1847 Patients

Program: Oral and Poster Abstracts
Type: Oral
Session: 902. Health Services Research—Malignant Conditions (Lymphoid Disease) II
Hematology Disease Topics & Pathways:
SARS-CoV-2/COVID-19, Coronaviruses, Adult, Diseases, Pediatric, Lymphoid Malignancies, Study Population, Clinically relevant, Myeloid Malignancies
Monday, December 7, 2020: 2:15 PM

Abi Vijenthira, MD1,2, Inna Gong, MD2*, Thomas A Fox, BSc, MSc, MRCP3*, Stephen Booth4*, Gordon Cook, MB ChB, PhD5*, Bruno Fattizzo, MD6*, Fernando Martín Moro7*, Jerome Razanamahery, MD8*, John Riches, MD, PhD9,10, Jeffrey I. Zwicker, MD11, Rushad Patell, MBBS12, Marie Christiane Vekemans13*, Lydia Scarfo14*, Thomas Chatzikonstantinou15*, Halil Yildiz, MD16*, Raphael Lattenist, MD16*, Ioannis Mantzaris, MD, MS17, William Wood, MD18* and Lisa K. Hicks, MD, MSc19,20

1Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
2Department of Medicine, University of Toronto, Toronto, ON, Canada
3University College London Hospitals NHS Foundation Trust, London, United Kingdom
4Churchill Hospital, Oxford, ENG, GBR
5Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom
6UOC Ematologia, Fondazione IRCCS Ca' Grande Ospedale Maggiore Policlinico and University of Milan, Milano, Milano, Italy
7Hematology and Hemotherapy, Hospital Universitario Ramón y Cajal, Madrid, Spain
8Besancon University Hospital, Besancon, France
9Centre, Barts Cancer Institute, London, United Kingdom
10The Francis Crick Institute, London, United Kingdom
11Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA
12Beth Israel Deaconess Medical Center, Boston, MA
13Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Bruxelles, Belgium
14Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy
15Hematology Department and HCT Unit, George Papanicolaou Hospital, Thessaloniki, GRC
16Université catholique de Louvain, Louvain-la-Neuve, Belgium
17Hematology/Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY
18University of North Carolina at Chapel Hill, Chapel Hill, NC
19Li Ka Shing Knowledge Institute, University of Toronto, Toronto, ON, Canada
20Division of Hematology/Oncology, St. Michael's Hospital, Toronto, ON, Canada

Introduction: Clinical outcomes for patients with hematologic malignancy and COVID-19 have not been aggregated. We completed a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients.

Methods: We searched Pubmed and EMBASE up to July 25, 2020, to identify reports of patients with hematologic malignancy and COVID-19 (including papers where the patients with hematologic malignancy were a subset of the total study population). The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included pooled estimates for the risk of ICU admission, mechanical ventilation, and non-invasive ventilation in hospitalized patients.

Mortality data were stratified by age, treatment status, and malignancy subtype. For treatment status, “systemic anti-cancer therapy (SACT)” was defined as patients on any anti-cancer therapy. “Cytotoxic SACT” was defined as patients on cytotoxic therapy only. “Not on treatment” was defined as patients on observation or those who were at least 28 days beyond their last active treatment.

Sensitivity analyses were conducted on the primary outcomes limiting to studies with low risk of bias, and to studies including both outpatients and hospitalized patients. Due to data limitations, only the primary outcome was assessed for pediatric studies. Pooled prevalence and risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model using MetaXL and Revman 5.4 software.

Results: A total of 25 adult studies and 4 pediatric studies comprising 1847 patients from China, Europe, the United Kingdom, and North America were included (Figure 1 and Table 1). The majority of patients were hospitalized (83%). The overall risk of death amongst all patients was 36% (95% CI 31-41, N=1763), and amongst hospitalized patients was 40% (95% CI 36-45, 24 studies with 1295 patients) (Figure 2). Patients aged >60 years had a significantly higher risk of death than patients <60 years (46% vs. 26%, RR 1.56, 95%CI 1.15-2.13, N=597) (Figure 3). The pooled risk of death in pediatric patients was 4% (95% CI 1-9, N=102) (Figure 2).

The risk of ICU admission among hospitalized adult patients was 23% (95% CI 17-29, N=1165); mechanical ventilation 16% (95% CI 12-21, N= 826); and non-invasive ventilation 16% (95% CI 9-26%, N=373).

The estimated RR of death among patients on SACT compared to no treatment was 1.22 (95% CI 0.84-1.78; N=457, Figure 3a). The RR of death among patients on cytotoxic SACT versus no treatment was similar at 1.29 (95% CI 0.78-2.15; N=176, Figure 3b).

All subgroups of hematologic malignancy had high risks of overall mortality: acquired bone marrow dysfunction syndromes 57% (95% CI 42-72, 11 studies, 42 patients); leukemias 44% (95% CI 31-58, 15 studies, 159 patients), plasma cell dyscrasias 38% (95% CI 29-47, 18 studies, 387 patients); lymphomas (including CLL) 32% (95% CI 26-38, 16 studies, 696 patients); lymphomas (excluding CLL) 32% (95% CI 18-48, 11 studies, 156 patients); CLL 31% (95% CI 24-39, 13 studies, 457 patients); myeloproliferative neoplasms 37% (95% CI 25-49, 9 studies, 62 patients).

Sensitivity analysis including only studies with a low risk of bias showed a similar estimate for risk of death among all patients (37% (95% CI 31-42, 20 studies with 1412 patients)) compared to all studies. Sensitivity analysis including only studies reporting on a combination of outpatients and hospitalized patients also showed a similar estimate for risk of death among all patients (38% (95% CI 32-44), 11 studies with 1214 patients) compared to all studies.

Conclusion: Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, appear to experience a high risk of dying (pooled risk estimate 36%). Older patients experience higher mortality, and pediatric patients appear to be relatively spared. Importantly, based on the observational data available to date, recent cancer treatment does not appear to significantly increase the risk of dying. These data highlight the need for robust strategies to prevent patients with hematologic malignancy from contracting COVID-19, and may help inform discussions about prevention strategies, treatment, and goals of care.

Disclosures: Cook: Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; IQVIA: Research Funding; Sanofi: Consultancy; Amgen: Consultancy; Roche: Consultancy; Karyopharm: Consultancy. Zwicker: Dova: Honoraria, Other: Advisory board; Portola: Honoraria, Other: Advisory board; Incyte: Research Funding; Quercegen: Research Funding; Parexel: Consultancy; Sanofi: Consultancy; CSL: Consultancy; Pfizer/BMS: Honoraria, Other: Advisory board. Scarfo: Gilead: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Wood: Pfizer: Research Funding; Best Doctors/Teladoc: Consultancy; Koneksa Health: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Elektra Labs: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ASH Research Collaborative: Honoraria; Genentech: Research Funding. Hicks: Gilead Sciences: Research Funding.

*signifies non-member of ASH