Immunological Responses to COVID-19 Vaccination in Hematologic Malignancies

Patients with haematologic malignancies exhibit a spectrum of immunodeficiencies that profoundly affect their responses to COVID-19 vaccines. Malignancies of the lymphoid and myeloid lineages, as well as treatments that deplete B cells or suppress immune function, lead to reduced seroconversion rates, lower antibody titres and, in many cases, preserved but variably robust T cell immunity. Vaccine type, dosing interval and prior therapies—particularly anti-CD20 antibodies and Bruton tyrosine kinase inhibitors—emerge as key determinants of humoral response. In contrast, T cell responses often remain detectable even when antibody production is impaired, offering a critical layer of protection against severe disease. Boosters can augment both antibody levels and cellular immunity, though durability varies by underlying disease, age and treatment regimen. Collectively, this body of work underlines the need for personalised vaccination strategies, monitoring of immune parameters and exploration of tailored immunogens to safeguard this high-risk population.

Research from Nature Portfolio

Recent studies have characterised the dual axes of humoral and cellular immunity following standard mRNA or viral-vector vaccination in patients with immune-suppressive disease states, including those with haematologic malignancies. Across thousands of participants, up to 40% failed to produce anti-spike antibodies after two doses, while a majority retained SARS-CoV-2-specific T cell responses, albeit at reduced magnitude in transplant recipients or those undergoing intense immunosuppression. Vaccine modality influenced outcome: mRNA regimens yielded higher antibody titres but somewhat lower cellular responses compared with adenoviral platforms. Clinical phenotypes at greatest risk of vaccine failure—such as those on anti-CD20 therapy, recent stem cell transplant or dialysis—were identified as candidates for enhanced prophylaxis.

A pioneering Phase I/II trial of a peptide-based T cell activator in B cell–deficient patients demonstrated that a single subcutaneous dose elicited multifunctional T helper type 1 CD4+ responses to multiple SARS-CoV-2 epitopes. This approach proved safe, induced broad cross-variant T cell immunity exceeding that elicited by spike-only vaccines and holds promise as a complementary strategy when humoral responses are absent.

Immunological Responses to COVID-19 Vaccination in Hematologic Malignancies publication trend

The graph below shows the total number of articles in immunological responses to covid-19 vaccination in hematologic malignancies across all publications each year (not limited to Nature Index journals).

Technical terms

Hematologic malignancy: Cancer of blood-forming tissues, including leukaemias, lymphomas and myeloma, often compromising immune function.

Seroconversion: The development of detectable specific antibodies in the blood following vaccination or infection.

T cell immunity: Protection mediated by T lymphocytes, essential for viral clearance and long-term immunological memory.

Bruton tyrosine kinase inhibitor (BTKi): A targeted agent in chronic lymphocytic leukaemia that can impair B cell maturation and vaccine-induced antibody responses.

Peptide-based T cell activator: A vaccine modality composed of selected viral peptides designed to stimulate broad T cell responses, particularly in patients with impaired B cell function.

References

1. SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease. Nature Medicine (2023).
2. A 3-week pause versus continued Bruton tyrosine kinase inhibitor use during COVID-19 vaccination in individuals with chronic lymphocytic leukaemia (IMPROVE trial): a randomised, open-label, superiority trial. The Lancet Haematology (2025).
3. Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency. Nature Communications (2023).
4. Fifth-week immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: preliminary data from a single institution. Journal of Hematology & Oncology (2021).
5. Antibody responses after first and second Covid-19 vaccination in patients with chronic lymphocytic leukaemia. Blood Cancer Journal (2021).