Immune Response to COVID-19 Vaccine in Children With Cancer

Source: Body A, Lal L, Downie P, et al. Immune response to COVID-19 vaccination in children with cancer. Pediatrics. 2025;156(3): e2024070209; doi: 10.1542/peds.2024-070209.Investigators from multiple institutions in Australia conducted a prospective study to evaluate the immune response to COVID-19 vaccination in children and adolescents with cancer. Study participants were patients ≤19 years old with solid or hematological cancers who were enrolled at 3 cancer centers in Australia. None of the participants previously had received COVID-19 vaccine. Data on demographics, type of cancer, and whether the patient was currently receiving, or had received, chemotherapy were collected. Participants received 2–3 doses of COVID-19 BNT162b2 vaccine. Blood specimens were obtained prior to the first and second doses of the vaccine, 1 month after dose 2, and either 3 months after dose 2 or 1 month after the third dose, if administered. The primary study outcome was neutralizing antibody (Nab) titers, with a titer ≥1:20 considered positive. The proportion of participants with valid results who had a positive titer after each vaccine dose was calculated. Rates of positivity also were determined in patients with hematological or solid cancers. The secondary outcome was interferon-gamma (IFN-gamma) level in response to COVID-19 Spike antigen, with a level ≥10 pg/mL considered a positive response. Data on adverse events also were collected.A total of 113 participants were enrolled. The median age of study patients was 13 years, and 67% had hematological cancers. At baseline, 77 (68%) participants were currently on anticancer treatment, and 35 (31%) were previously on treatment, including 18 (16%) who completed treatment >6 months prior to their first dose of COVID-19 vaccine. Nab titers were positive in 66% of patients with evaluable data after 2 doses and 80% after 3 doses. Among those with hematological cancers, 65% and 79%, respectively, had positive titers after 2 and 3 doses. For those with solid cancers, 68% and 82%, respectively, had positive Nab titers. The rate of positive Nab titers for patients currently on anticancer treatment was 62% after 2 doses and 76% after 3 doses, compared to 78% and 100%, respectively, for those who had been treated previously. At baseline, 39% of patients had a positive IFN-gamma response to Spike antigen, increasing to 59% after dose 1, 69% after dose 2, and 74% after the third dose of COVID-19 vaccine. There were 22 participants who developed fever possibly attributed to COVID-19 vaccine, including 7 with febrile neutropenia. No patients had myocarditis or pericarditis, and none had to delay cancer treatment because of COVID-19 vaccination.The authors conclude that most children and adolescents with cancer responded to COVID-19 vaccination, including those currently on anticancer treatment.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.COVID-19 vaccines for infants, children, and adolescents have been in the news recently.1,2 For those 6 months through 18 years of age, the Advisory Committee on Immunization Practices recommends a shared clinical decision-making approach.1 The American Academy of Pediatrics recommends COVID-19 vaccination for all children 6 through 23 months of age who do not have contraindications, and for all children 2 through 18 years of age who are in risk groups.2 Children 2 through 18 years of age not included in the risk groups and whose parent or guardian desires their protection from COVID-19 should be offered vaccination.The authors focused on children with cancer, a risk group with substantial morbidity from COVID-19.3-5 Their study was small (113 patients), so it was not powered to detect rare serious adverse events such as myocarditis.6 Side effects (fever, mucositis, headache) were transient and did not delay cancer therapy. Interruptions in cancer treatment often impair long-term cancer outcomes.5 For children with cancer, the risk-benefit analysis favored receipt of COVID-19 vaccination.The next question was the timing of COVID-19 vaccine receipt for children with cancer. Vaccination against influenza is recommended for children with cancer, even while receiving active chemotherapy, because they are at high risk of hospitalization and death from influenza, and even a diminished immune response offers some protection.7 The authors conducted this study in 2021– 2022 in Australia at the peak of the COVID-19 pandemic and followed a similar strategy. They studied neutralizing and binding antibody responses that have been demonstrated to be immune correlates of protection against infection by the SARS-CoV2 coronavirus.8 Protective antibody responses to the COVID-19 vaccine were demonstrated in most children with cancer despite anticancer treatment, suggesting that vaccination does not require deferral until treatment completion.COVID-19 vaccines are safe and immunogenic for children with cancer, even those receiving anticancer treatment.Of course, a follow-up study to ascertain COVID-19 vaccine-induced protection against clinical disease in children with cancer would be most compelling.