Impaired responses to COVID-19 vaccination in patients with lymphoma receiving B-cell–directed therapies

September 2021 Prevention Jolien Blokken

As treatment with B-cell-directed therapies may adversely affect the production of antibodies in response to COVID-19 vaccination, it is highly likely that patients treated with these drugs have impaired humoral responses to vaccination. However, results from a recent study now indicated that COVID-19 vaccination at least 9 months from the last B-cell-directed treatment may result in improved antibody titers for lymphoma patients.

Expert opinion of dr. Bert Heyrman, Haematologist, ZNA

We are all aware that our patients suffer from an impaired response to vaccination, especially those patients receiving B-cell depleting regimens. This is a daily topic addressed during our consultations. This article confirms impaired responses and can help in directing patients towards revaccination and speak with confidence about foreseen timelines.”

Despite the fact that patients with haematologic malignancies are at an increased risk of morbidity and mortality when infected with SARS-CoV-2, patients who were actively receiving cancer treatment where excluded from clinical trials with the approved vaccines. Treatment with B-cell–directed therapies may adversely affect the production of antibodies in response to SARS-CoV-2 vaccination in patients with lymphoma because of B-cell depletion and/or disruption of the B-cell receptor signalling pathway. Therefore, Ghione et al. evaluated the antibody response to the COVID-19 vaccines in patients with B-cell lymphoma (BCL) who were either actively receiving or previously received B-cell-directed therapy. Researchers assessed the impairment of antibody production and hypothesised that the ability to respond to COVID-19 vaccines would be restored at a certain time after treatment discontinuation.

Study design

The study enrolled lymphoma patients who were actively receiving or had previously completed B-cell-directed therapy and had received full vaccination with a COVID-19 vaccine (N= 77). In addition, the vaccines’ efficacy was also monitored in patients with lymphoid malignancies who were either under observation or receiving non-B-cell-directed therapy (N= 9) and in individuals without lymphoma (healthcare personnel from the Roswell Park Comprehensive Cancer Center and in nursing homes [N= 154] or nursing home residents older than 65 years [N= 47]). Serum samples were collected within 2 to 8 weeks after the final dose of the vaccine.

Humoral responses to COVID-19 vaccination

Antibodies against the spike SARS-CoV-2 virus protein were detected in all healthcare personnel (HCP) and in 6 of 7 (85.7%) patients without BCL vaccinated during active cancer treatment. In contrast, however, only 4 of 41 (9.7%) patients with BCL developed antibodies while actively receiving or within 3 months of completing B-cell depleting therapy. Patients with BCL who were receiving or had completed B-cell-directed therapy were divided in 4 temporal groups: receiving the vaccine (I); on active treatment or within 3 months after treatment, (II) 3-6 months, (III) 6-9 months or (IV) more than 9 months after B-cell directed therapy. None of the patients demonstrated a significant IgM response to vaccination. In contrast, the IgG response in the four BCL groups was significantly different (p= 0.0001). The comparison of patients with ongoing treatment or vaccinated within 3 months from the last treatment to patients vaccinated more than 9 months after the last treatment showed a marked difference in the IgG response (p= 0.0001; 95%CI: 12.98-24.78). Median cut-off index IgG production was 0.13 (range 0.0-12.4) for the recent treatment group vs. 20.7 (range 0.1-63.8) for the second group (p= 0.0001; 95%CI: 18.8-30.92). As expected, the IgA response was less pronounced for all groups of patients. However, there was also a significant difference in IgA levels of patients on active treatment or vaccinated within 3 months from the last treatment to patients with BCL vaccinated more than 9 months after the last treatment (p= 0.0005; 95%CI: 0.14-0.46). Overall, in the cohort of BCL patients actively receiving B-cell-depleting agents or within 9 months of completing these treatments (N= 52), only 6 developed antibodies against the SARS-CoV-2 virus, regardless of the type of vaccine that was used.

Conclusion

Results from this study suggest that SARS-CoV-2 vaccination at least 9 months after the last B-cell-directed treatment may result in improved antibody titers. This finding is important to further establish a possible timeline for revaccination of these patients. Furthermore, these results highlight the importance of herd immunity in the general community to protect immunocompromised patients.

Reference

Ghione P, Gu JJ, Attwood K, et al. Impaired humoral responses to COVID-19 vaccination in patients with lymphoma receiving B-cell–directed therapies. Blood. 2021;138(9):811-814.

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