A new study conducted by researchers at Winship Cancer Institute of Emory University finds that COVID-19 vaccines are much less effective for patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL), particularly those age 65 and older. After vaccination, many of these patients produced low or no antibodies that bind or neutralize SARS-CoV-2 and its variants of concern, especially Omicron.
The study, led by Andres Chang, MD, PhD, and colleagues, was recently reported in the Journal of Clinical Oncology. Chang, a hematologist specializing in treating patients with hematological malignancies, including leukemia and lymphoma, is a member of the Cancer Immunology research program at Winship and an instructor in the Department of Hematology and Medical Oncology at Emory University School of Medicine.
The study of 121 patients with NHL/CLL found that 29.6% to 52.9% of patients showed no seroconversion at any given point in time. (Seroconversion is the production of antibodies in response to an antigen; antibodies are proteins used by the immune system to identify and neutralize antigens, which are usually foreign substances like parts of viruses and bacteria.) Patients with NHL/CLL who received anti-CD20-directed therapies, which are commonly used to treat NHL/CLL, within one year before initial vaccination showed the most profoundly impaired response to vaccination. Chang explains, "This is because anti-CD20-directed therapies deplete B cells, which are the cells responsible for making antibodies. These types of therapies tend to stay in the patient's body for weeks, and thus it takes months for someone to have detectable circulating B cells in their blood again after undergoing such therapy."
Individuals treated with novel lymphoma therapies – such as Bruton's tyrosine kinase and Bcl-2 inhibitors (BTKi and Bcl-2i) – also appeared to have lower antibody levels after vaccination compared with either untreated patients or those treated with conventional cytotoxic chemotherapies. "There is no direct data that explains why patients on novel lymphoma therapies may have lower antibody levels after vaccination," says Chang. "However, novel lymphoma therapies, particularly BTK inhibitors, can limit the activation of normal B cells, which may lead to lower antibody levels."
What strategies, in Chang's view, would improve antibody responses after vaccination in patients with NHL/CLL? He says, "Unfortunately, those with no detectable B cells are unlikely to mount an antibody response. However, finding the optimal timing of vaccination and the best vaccination regimen are key to improving antibody responses after vaccination in this population. Our research suggests that looking at number of circulating B cells in the blood can be predictive of vaccine responses, which may help decide on the best timing of vaccination."
Further study needed
Chang also notes that there is a "small report suggesting that vaccinating before starting anti-CD20-directed therapy can help get better responses," though he says it is still unclear as to whether those responses are long-lasting. He and his team are also looking at data on the effect of booster vaccines in this population to determine how beneficial those additional doses might be. They are also exploring whether these patients may still have a protective T cell response.
Chang says the study's findings stress the importance of instituting additional vaccine doses and/or early therapy with oral antiviral agents or passive immunization with anti-SARS-CoV-2 monoclonal antibodies to try to better protect this patient population. "Overall," he says, "our findings stress the importance of performing further studies to understand the immune responses in lymphoma patients while prioritizing antivirals and passive immunization measures to protect this population."
The study's senior author, Rafi Ahmed, PhD, co-leader of Winship's Cancer Immunology Research Program and director of the Emory Vaccine Center, says, "Our studies looking at COVID-19 vaccine responses in cancer patients represent a wonderful and highly synergistic collaboration between the Emory Vaccine Center and the Winship Cancer Institute. We hope to build upon these collaborations to understand how vaccination strategies can be optimized for cancer patients."