In a study conducted by Dr. Susanne Saussele and colleagues from the University Hospital Mannheim and reported during the 2021 American Society of Hematology (ASH) Annual Meeting, the German research team emphasized a potential of third booster COVID-19 vaccine dose exploration within clinical trials in patients with haematological disorders. In their study, a remarkable group of patients were measured with no or low immune response after second COVID-19 vaccine dose, especially those with lymphoid neoplasms. Of those who tested negative for vaccine-related antibodies, most were on active therapy. The study team underlined that further explorations are needed with focus on potential risk of COVID-19 infections despite full vaccination.

Severe COVID-19 associated with high mortality is more likely in patients with haematological malignancies compared to the general population. Due to immune defects related to the primary disease and/or to immunosuppressive treatment, vaccine efficacy may be reduced in these patients with limited data available.

In this study, the researchers from the University Hospital Mannheim evaluated vaccination-related antibody response to BNT162b2, mRNA-1273, and ChADOx1 vaccine in patients with haematological disorders. They reported antibody levels at least 2 weeks after COVID-19 vaccination from the interim analysis of a prospective, observational single-centre study.

They used an FDA/CE approved electrochemiluminescent assay to quantify antibodies, pan immunoglobulins (Ig), including IgG, against the receptor binding domain of the SARS-CoV-2 spike protein. The assay has a measurement range of 0.4 to 250 U/mL, with a concentration ≥0.8 U/ml considered as positive. They analyzed data for patients without detection of anti-N (nucleocapsid) SARS-CoV-2 antibody. The antibody levels were measured at least 14 days (median, 58 days) after the second vaccine dose.

In the abstract, the research team reported that between February 2021 and July 2021, 175 patients with haematological disorders were included in this study. The median age was 66 years (range 21-90), and 81 (46.3%) were female. Most patients received BNT162b2 (n=134), mRNA-1273 (n=19), ChADOx1 (n=12), or the first vaccine dose of BNT162b2 and the second ChADOx1 (n=10).

Overall, 145 of 175 patients (82.9%) were diagnosed with a haematological malignancy, of those 108 with myeloid neoplasms, 37 with lymphoid neoplasms, while 30 patients had a non-malignant haematological disease, in particular 24 autoimmune disease and 6 benign. In total, 124 patients (70.1%) were on active therapy, and 51 patients (29.1%) were previously treated or treatment naïve.

Vaccine-related antibody response was positive in 148 of 175 patients (84.6%) with a median level of 208.6 U/mL (range, 0.8-250.00) and negative in 27 of 175 patients (15.4%). Distribution of the negative cohort regarding the disease subgroups were as followed: myeloid neoplasms in 7 of 27 patients (25.9%), lymphoid neoplasms in 16 of 27 (59.3%), non-malignant haematological disease in 4 of 27 (14.8%). Within the negative cohort, 21 of 27 patients (77.8%) were on active therapy, and 6 of 27 (22.2%) were previously treated or treatment naïve.

In myeloid neoplasms, patients with classical myeloproliferative neoplasm had the highest negative result for antibodies with 4 of 7 (57.1%) followed by myelodysplastic syndrome in 2 of 7 (28.6%). All patients with chronic myeloid leukaemia had a measurable immune response.

In lymphoid neoplasms, patients with low-grade non-Hodgkin lymphoma (NHL), predominately chronic lymphocytic leukaemia had the highest negative antibody result, 13 of 16 (81.3%) followed by high-grade NHL in 4 of 8 (50%) who predominately had diffuse large B-cell lymphoma.

In non-malignant haematological diseases, only patients with autoimmune diseases had a negative result.

Among patients included in this study, those who tested negative for vaccine-related antibodies, most (71%) were on active therapy. Therapies correlated with a negative response were rituximab, ibrutinib, acalabrutinib, and ruxolitinib.

Although it is encouraging that most of the study participants showed antibody response, the findings also suggest the COVID-19 vaccination should be complemented with other precaution measures in patients with haematological disorders.

The study team plans to measure level of antibodies for at least a year and to assess a rate of breakthrough infections and response to vaccine boosters.   


Rotterdam J, Thiaucourt M, Schwaab J, et al. Antibody Response to Vaccination with BNT162b2, mRNA-1273, and ChADOx1 in Patients with Myeloid and Lymphoid Neoplasms. Abstract 218; 2021 ASH Annual Meeting, 10-14 December.