Patients Treated With Chemotherapy and B Cell–Targeting Agents Show Impaired Serological Response to COVID-19 Vaccination

A cohort study of patients with haemato-oncological diseases and a control group of healthcare workers, performed in Austria and Italy, suggests that patients with cancer are able to develop SARS-CoV-2-specific antibodies. Based on two independent cohorts from an academic centre and a community hospital in a rural area, the study investigators found lower antibody levels in patients than in a healthcare workers control group, and specific patients subgroups who received chemotherapy and B cell–targeting agents, showed a particularly impaired serological response. The patients included in this study have various solid tumours and haematological malignancies and were treated by different antineoplastic treatments, providing real-life insights. However, the study team who published the findings on 30 September 2021 in the JAMA Oncology underlines a need for dedicated studies to evaluate the effectiveness of COVID-19 vaccination in patients with cancer.

The authors emphasised that immunocompromised patients were not included in the studies on mRNA or viral vector COVID-19 vaccines. Furthermore, large-scale real-life studies that assess the response of patients with haemato-oncological diseases to COVID-19 vaccines are rare. The study team led by Prof. Matthias Preusser of the Department of Medicine I, Division of Oncology, Medical University of Vienna in Vienna, Austria aimed to identify factors associated with antibody responses in patients with solid tumours and haematological malignancies and compare them with healthcare workers.

They analyzed 901 samples from 595 patients treated in their institutions for haematological and solid malignant tumours between October 2020 and May 2021 and 58 healthcare workers. Ongoing treatments included cytotoxic chemotherapy, immune checkpoint inhibitors, targeted therapies such as tyrosine kinase inhibitors and other monoclonal antibodies, as well combination treatments. Total anti–SARS-CoV-2 nucleocapsid (anti-NC) and antispike protein (anti-S) antibodies were measured retrospectively.

Among included patients, there were 320 women (53.8%) and 275 men (46.2%) with median age of 67 years (range, 19-96). Among 58 healthcare workers there were 40 women (69.0%) and 18 men (31.0%) with median age of 42 years (range, 24-60). Previous SARS-CoV-2 infection was documented in 43 of 595 patients (7.2%), while anti-NC antibodies that suggested previous infections were observed in 49 of 573 evaluable patients (8.6%).

In both cohorts, anti-S antibody levels were higher in fully vaccinated patients compared with patients who received 1 vaccine dose. After the first vaccination, patients with haematological malignancies who received B cell–targeting agents had lower anti-S levels with median 1.6 AU/mL (range, 0-17 244 AU/mL) than patients who received other therapies with median 191.6 AU/mL (range, 0-40 000) and p value < 0.001, or patients with solid tumours with median 246.4 AU/mL (range, 0-40 000 AU/mL) and p value < 0.001.

Anti-S levels after the first vaccination differed according to ongoing antineoplastic treatment modalities, with the lowest median levels recorded in patients who received chemotherapy alone, 157.7 AU/mL (range, 0-40 000 AU/mL) or in combination with immunotherapy, 118.7 AU/mL (range, 14.1-38 727 AU/mL) and the highest levels in patients with no ongoing antineoplastic treatment, median 634.3 AU/mL (range, 0-40 000 AU/mL) with p value of 0.01.

Antibody levels after full immunisation were higher in healthcare workers with median 2500 U/mL (range, 485-2500 U/mL) than in patients with cancer with median 117.0 U/mL (range, 0-2500 U/mL) and p value < 0.001.

The authors acknowledged some limitations of their study. In particular, immunoassays from different manufacturers were used in the Vienna and the Meran cohorts. Retrospective study design is associated with heterogeneous cohorts and small numbers in specific subgroups. Furthermore, times between vaccination and sampling varied in the Vienna patient and healthcare workers cohorts, so seroconversion may not have been measurable at the time of sampling, considering the kinetics of humoral immune responses.

The authors concluded that their findings suggest lower SARS-CoV-2 antibody levels in patients with cancer after vaccination compared with vaccinated healthcare workers, and particularly weak seroconversion in specific subgroups, highlighting the need for dedicated COVID-19 vaccination studies in patients with cancer.

The study was funded by the research budgets of the Medical University of Vienna and Südtiroler Sanitätsbetrieb.


Mair MJ, Berger JM, Berghoff AS, et al. Humoral Immune Response in Hematooncological Patients and Health Care Workers Who Received SARS-CoV-2 Vaccinations. JAMA Oncology; Published online 30 September 2021. doi:10.1001/jamaoncol.2021.5437