REDUCED HUMORAL IMMUNE RESPONSE AFTER BNT162B2 COVID-19 MRNA VACCINATION IN CANCER PATIENTS UNDER ANTI-NEOPLASTIC TREATMENT

Peeters, M.; Verbruggen, L.; Teuwen, L.; Vanhoutte, G.; Kerckhove, S. Vande; Peeters, B.; Raats, S.; Van der Massen, I.; De Keersmaecker, S.; Debie, Y.; Huizing, M.; Pannus, P.; Neven, K.; Ariën, K.K.; Martens, G.A.; Van Den Bulcke, M.; Roelant, E.; Desombere, I.; Anguille, S.; Goossens, M.; Vandamme, T.; van Dam, P.

BACKGROUND: Cancer patients are at higher risk of developing severe COVID-19. However, safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment is unclear. PATIENTS AND METHODS: In this interventional prospective multi-cohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted- or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Vaccine safety and efficacy (until three months post-booster) were assessed. Anti-SARS-CoV-2 receptor binding domain (RBD) antibody levels were followed over time (until 28 days post-booster) and in vitro SARS-CoV-2 50% neutralization titers (NT50) towards the wild-type Wuhan strain were analyzed 28 days post-booster. RESULTS: Local and systemic adverse events (AEs) were mostly mild to moderate (only 1-3% of patients experiencing severe AEs). Local, but not systemic, AEs occurred more frequently after booster dose. 28 days post-booster vaccination of 197 cancer patients, RBD-binding antibody titers and NT50 were lower in the chemotherapy group (234.05IU/mL [95%CI 122.10-448.66] and NT50 of 24.54 [95% CI 14.50-41.52]) compared to healthy individuals (1844.93IU/mL [95% CI 1383.57-2460.14] and NT50 of 122.63 [95% CI 76.85-195.67]), irrespective of timing of vaccination during chemotherapy cycles. Extremely low antibody responses were seen in hematology patients receiving rituximab, only two patients had RBD-binding antibody titers necessary for 50% protection against symptomatic SARS-CoV-2 infection (<200IU/mL) and only one had NT50 above the limit of detection. During the study period, five cancer patients tested positive for SARS-CoV-2 infection, including a case of severe COVID-19 in a patient receiving rituximab, resulting in a 2-week hospital admission. CONCLUSION: The BNT162b2 vaccine is well-tolerated in cancer patients under active treatment. However, the antibody response of immunized cancer patients was delayed and diminished, mainly in patients receiving chemotherapy or rituximab, resulting in breakthrough infections.