Poor Neutralizing Antibody Responses in 132 Patients with CLL, NHL and HL after Vaccination against SARS-CoV-2: A Prospective Study

Terpos, Evangelos; Gavriatopoulou, Maria; Fotiou, Despina; Giatra, Chara; Asimakopoulos, Ioannis; Dimou, Maria; Sklirou, Aimilia D.; Ntanasis-Stathopoulos, Ioannis; Darmani, Ismini; Briasoulis, Alexandros; Kastritis, Efstathios; Angelopoulou, Maria; Baltadakis, Ioannis; Panayiotidis, Panayiotis; Trougakos, Ioannis P.; Vassilakopoulos, Theodoros P.; Pagoni, Maria; Dimopoulos, Meletios A.

SIMPLE SUMMARY: The urgency of the COVID-19 pandemic has led to accelerated vaccine development within less than a year. Emerging data suggest that the ability of patients with hematological malignancies to form an adequate number of antibodies in response to vaccination for SARS-CoV-2 is suboptimal. In this context, we evaluated the ability of 132 patients with Chronic Lymphocytic Leukemia, Non-Hodgkin’s Lymphoma and Hodgkin’s Lymphoma to elicit an adequate immune response to the BNT162b2 vaccine. Vaccination with two doses of the BNT162b2 vaccine led to lower production of neutralizing antibodies against SARS-CoV-2 in these patients compared with healthy controls. Being on active treatment for the underlying disease was an independent prognostic factor for suboptimal antibody response. This finding underlines the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures. ABSTRACT: Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton’s tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.