Mortality of COVID-19 in Patients with Hematological Malignancies Versus Solid Tumors: A Systematic Literature Review and Meta-Analysis

Background: As of May 2022, the COVID-19 pandemic has been the cause of 6.3 million deaths worldwide and over one million deaths in the United States. Cancer patients are more vulnerable to COVID-19 compared to the general population, but it remains unclear which types of cancer have the highest risk of COVID-19-related mortality. This study examines mortality rates for those with hematological malignancies (Hem) versus solid tumors (Tumor).

Methods: PubMed and Embase were systematically searched for relevant articles using Nested Knowledge software (Nested Knowledge, St Paul, MN). Articles were eligible for inclusion if they reported mortality for Hem or Tumor patients with COVID-19. Articles were excluded if they were not published in English, non-clinical studies, had insufficient population/outcomes reporting, or were irrelevant. Baseline characteristics collected included age, sex, and comorbidities. Primary outcomes were all-cause and COVID-19-related in-hospital mortality. Secondary outcomes included rates of invasive mechanical ventilation (IMV) and intensive care unit (ICU) admission. Effect sizes from each study were computed as logarithmically transformed odds ratios (ORs) with random effects, and Mantel-Haenszel weighting. The between-study variance component of random-effects models was computed using restricted effects maximum likelihood estimation, and 95% confidence intervals (CIs) around pooled effect sizes were calculated using Hartung-Knapp adjustments.

Results: 12,057 patients were included in the analysis, with 2,714 (22.5%) patients in the Hem group and 9,343 (77.5%) patients in the Tumor group. The overall unadjusted odds of all-cause mortality were 1.64 times higher in the Hem group compared to the Tumor group (95% CI: 1.30-2.09) [Fig. 1]. This finding was consistent with multivariable models presented in moderate- and high-quality cohort studies, suggestive of a causal effect of cancer type on in-hospital mortality. Additionally, the Hem group had increased odds of COVID-19-related mortality compared to the Tumor group (OR=1.86 [95% CI: 1.38-2.49]) [Fig.2]. There was no significant difference in odds of Invasive Mechanical Ventilation or ICU admission between cancer groups (OR=1.13 [95% CI: 0.64-2.00] and OR=1.59 [95% CI: 0.95-2.66], respectively).

Discussion: The current study fills a gap in the literature by comparing mortality for patients with hematological versus solid cancers. While the mechanism of action is unclear, it is possible that the hematological manifestations of COVID-19 interact with the hematological cancer disease state to result in worse outcomes for these patients. COVID-19 is known to cause leukopenia, lymphopenia, and thrombocytopenia in those infected, which contribute to a prothrombotic state and can serve as predictors of patient outcome. D-dimer levels are also associated with thrombosis, and studies have shown that underlying cancer may elevate D-dimer levels for patients with COVID-19, increasing likelihood of severe illness or mortality. Furthermore, evidence shows that hematological cancer patients have a significantly lower seroconversion rate following COVID-19 vaccination compared to those with solid tumors, suggesting a weaker immune response upon infection with COVID-19.

Conclusions: Cancer is a serious comorbidity associated with severe outcomes in COVID-19 patients, with especially alarming mortality rates in patients with hematological malignancies, which are typically higher compared to patients with solid tumors. A meta-analysis of individual patient data is needed to better assess the impact of specific cancer types on patient outcomes and to identify optimal treatment strategies.

Hardy:Nested Knowledge: Current Employment, Current equity holder in publicly-traded company. Mebane:Superior Medical Experts: Consultancy, Other: Editing & drafting, Research Funding; Audubon PM: Consultancy, Other: Editing & Drafting, Research Funding. Kallmes:Nested Knowledge: Current Employment, Current equity holder in private company.