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COVID-19 Vaccine Responses Vary Among Hematological Malignancies

Key Takeaways

  • The primary outcome was the rate of seropositivity after 2 doses of a COVID-19 vaccine with rates of seropositivity after 1 dose, rates of positive neutralizing antibody (nAb), cellular responses and adverse events as secondary outcomes.

  • Two thirds of patients (67%) with hematological malignancies were seropositive after 2 doses of a COVID-19 vaccine.

  • Patients at highest risk of nonresponse included those with chronic lymphocytic leukemia (CLL) and those undergoing treatment with active targeted and anti-CD20 therapies.

  • New approaches for high-risk patients who are poor responders to vaccination are urgently required, the authors wrote.

Why This Matters

  • More than 80% of patients with hematological malignancies require hospitalization after infection with COVID-19, and more than 50% have severe disease. Mortality can be as high as 30%-40%.

  • Patients with hematological malignancies were excluded from vaccine clinical trials.

Study Design

  • The study was a meta-analysis of 44 studies of 7064 patients. It included 2331 who were analyzed after a first dose and 4733 after the second dose of any COVID-19 vaccine.

  • The authors analyzed data on humoral and cellular immune responses following vaccination. A humoral response (seropositivity) was defined as detectable levels of SARS-CoV-2 spike/receptor binding domain-specific immunoglobulin G (IgG). A cellular response was defined as an increase in SARS-CoV-2 specific CD4+/CD8+ T cells.

  • Risk of bias was assessed using the Newcastle-Ottawa Scale.

Key Results

  • The rate of seropositivity in hematology patients was 61% after 2 COVID-19 vaccine doses, and 67% in comparator studies. After a single dose, the rates were 51% and 37%, respectively.

  • Hematologic malignancy was associated with a lower likelihood of achieving seropositivity than healthy controls after 2 doses (odds ratio 0.05; P < .01), and after 1 dose (OR, 0.10; P < .01).

  • In 10 studies (22%), the rate of at least one systemic or local adverse event was reported. Overall, the pooled rate of at least one adverse event was 36% following 2 doses and 39% following a single dose.

  • Seropositivity rates after 2 doses of vaccine were highest among patients with acute leukemia and myelodysplastic syndromes (93%), followed by myeloproliferative neoplasm and chronic myeloid leukemia (87%-88%), and the lowest in CLL patients (51%).

  • Subgroup analyses showed the lowest seropositivity among patients receiving active treatment (28%), specifically current or previous 12-month treatment with anti-CD20 antibody (19%), targeted therapies (35%), and after CAR-T therapy (31%). Seropositivity rates were higher among patients not on active therapy (61%) or 12 or more months after completion of anti-CD20 therapy (62%).


  • The quality of the findings is moderate due to significant clinical and statistical heterogeneity in the included studies.

  • The immune response data does not necessarily reflect clinical efficacy of vaccination.

Study Disclosures

  • Authors have received research funding and honoraria from Pfizer, Merck Sharp and Dohme, CSL Behring, and Sanofi, as well as research funding from Gilead.

This is a summary of preprint research, “Immunogenicity of COVID-19 vaccines in patients with haematological malignancy: A systematic review and meta-analysis,” led by Benjamin W. Teh, PhD, a researcher at Peter MacCallum Cancer Centre and the University of Melbourne, Australia. It was published on in advance of peer review and is provided to you by Medscape.

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