COVID-19 vaccination least effective in patients with lymphoid malignancies

To date, little is known on the vaccination efficacy in patients with haematological diseases. A single-centre German study now demonstrates that a remarkable group of patients with haematological malignancies demonstrates no or low immune response after their second COVID-vaccination with BNT162b2, mRNA-1273 or ChADOx1 vaccines. Antibody production seems especially low in those patients with lymphoid malignancies.

Due to immune defects related to the primary disease and/or to immunosuppressive treatment regimes, COVID-19 vaccination efficacy may be reduced in patients with haematological diseases. In general, these patients demonstrated to have lower antibody titres after COVID-19 vaccination. However, data on patients with myeloid neoplasms are scarce. Therefore, a better understanding of the vaccine response among patients with haematological disease is mandatory.

Study design

The University of Heidelberg conducted a prospective, observational single-centre study between July and October 2021 that reports on antibody levels at least two weeks after COVID-19 vaccination. An FDA/CE approved electrochemiluminescent assay (ECLIA) (Elecsys®, Roche, Mannheim, Germany) was used to quantify antibodies, pan Ig (including IgG) against the receptor binding domain of the SARS-CoV-2 spike protein. The test also detects antibodies against the nucleocapsid antigen. The assay has a measurement range of 0.4 to 250 U/mL, with a concentration ≥0.8 U/ml considered as positive. Data were analysed for patients without detection of anti-nucleocapsid SARS-CoV-2 antibody (i.e., without having passed SARS-CoV-2 infection). All tests were performed according to the manufacturer's instructions in an accredited laboratory at the University Hospital Mannheim.

Results

In total, antibodies of 373 patients were measured. The median age of study participants was 64 years and 44% were female. Patients were vaccinated with BNT162b2 (BioNTech/Pfizer, 77%), mRNA-1273 (Moderna, 10%), ChADOx1 (AstraZeneca, 7%), or got the first vaccination with ChaDox1 and the second with BNT162b2 (6%). The median time between vaccination and analysis was 12 weeks. In total, 91% of patients were diagnosed with a malignant haematological disease, of which 67% had a myeloid neoplasm and 33% had a lymphoid neoplasm. As a control, patients with other haematological disease were included. Of these 35 patients (9%), 26 patients had an autoimmune disease and 9 had a benign haematologic disease. Sixty-one percent of patients were on active therapy, while the remaining patients were previously treated or treatment naïve.

Vaccination-related antibody response was below 0.8 U/ml, and therefore negative, in 56 patients (15%). A positive vaccination-related antibody response was observed in the 317 other patients, with a mean value of 197 U/ml. In total, 89 patients had an antibody response between 0.8 and 249 U/ml. Negative vaccination response was predominantly observed in lymphoid neoplasm (72%), reflecting 36% of the total cohort of patients with lymphoid neoplasm. Furthermore, 12 patients had a myeloid neoplasm (21%) and 4 an autoimmune disease (7%). Negative antibody response was predominant in indolent NHL (25 out of 60 cases) and aggressive NHL (8 out of 18 patients). In myeloid neoplasms, MPN was predominant with 6 out of 76 patients and in MDS (5 out of 16 patients). In CML, nearly no negative response was measured (1 out of 101 patients). Of the patients with a negative vaccination response, 39 patients (71%) were on active treatment (lymphoid, N= 26; myeloid, N= 9 and autoimmune, N= 4). Therapies associated with significant negative results were BTK inhibitors, immunoglobulins and rituximab, while tyrosine kinase inhibitors were associated with significant positive results. Five out of the six patients with MPN who had negative antibody response received ruxolitinib therapy.

Conclusion

There is a remarkable group of patients with haematological disease with no or low immune response after the second COVID-vaccination, especially in patients with lymphoid disease. Therapies associated with low response were rituximab, ibrutinib, acalabrutinib and ruxolitinib. In patients with CML, a positive seroconversion was measured in 99%. As a substantial number of patients with haematological diseases thus does not have an adequate antibody response, they might not have a sufficient protection against COVID-19. Therefore, these patients will benefit from ongoing protective measures and a priority vaccination of their family and caregivers should be considered to maximally protect these patients.

Reference

Rotterdam J, et al. Antibody Response to Vaccination with BNT162b2, mRNA-1273, and ChADOx1 in Patients with Myeloid and Lymphoid Neoplasms. Presented at ASH 2021; Abstract 218.