Humoral response to mRNA vaccines BNT162b2 and mRNA-1273 COVID-19 in chronic lymphocytic leukemia patients

ABSTRACT

Chronic lymphocytic leukemia (CLL) patients experience both humoral and cellular immune deficiency, with a reduced number of normal B lymphocytes, and hypogammaglobulinemia. Previous large studies on vaccination efficacy are scarce but it is well-established that CLL patients have a poorer response than normal subjects to vaccination and are at increased risk of infection. Efficacy of anti-SARS-Cov-2 vaccination in CLL has been recently published by the Israeli group (Herishanu, 2021) showing that among hematological malignancies, patients who presented CLL disease are the least responsive to vaccination. We have collected the results of a large cohort of 502 French patients after vaccination by either BNT162b2 or mRNA-1273 mRNA vaccine. Patients received 2 doses at a 4-week interval. For those who received the 3rd dose, the interval was usually longer (between 6 and 8 weeks after 2nd dose). The median time to sample collection for serology was 4 weeks, and IgG anti-SARS-CoV-2 Spike antibody levels were measured by commercially available tests. We evaluated patients after the 1st and 2nd doses and collected matched samples whenever possible. Patients who had a previous COVID-19 infection were analyzed separately. We evaluated 176 patients after the 1st dose and the global seroconversion rate was only 31% (55/176). We evaluated 455 patients after the 2nd dose, and the global rate of seroconversion was 54% (246/455). Matched samples after both first and second doses were available for 118 patients. In this cohort, among the 87 patients who were seronegative after the first dose, 42 patients (48%) became positive after the second dose. Most patients who remained seronegative after two doses, received the third dose. The administration of the third dose program started recently, therefore, to date, we have the results for 31 patients only. Among these patients, 18 remained negative after this 3rd dose, while 13 (42%) seroconverted. Therefore, if we extrapolate these data, it is expected that approximately only 70-75% of CLL patients will be protected by vaccination (either by two or three doses) at the end of the vaccination program. On the other hand, 40 patients who received at least one dose of vaccine had presented a COVID-19 infection before vaccination. In this group of patients, the humoral response was evaluated in 29 patients. All of them except one, presented very high anti-Spike antibodies titer, even after one dose, and the only patient who remained seronegative after vaccination was on prolonged anti-CD20 therapy for autoimmune thrombocytopenia. We also collected cases of COVID-19 infection post-vaccination. Nineteen patients presented a COVID-19 infection after vaccination, 11/19 presented the infection after the first dose, and 8/19 after the second dose. Among those eight patients, five presented the first symptoms within the first 2 weeks after the second dose and had a more severe COVID-19 infection while the three patients with a later onset of symptoms (4-6 weeks after vaccination) had very mild symptoms. All patients tested had no antibody response before COVID infection but had highly positive anti-Spike titers after infection. Currently, the COVID- 19 pandemic has settled down and it is difficult to know if the absence of post-vaccination COVID-19 infection is related to the slowing of the pandemic or if CLL patients are protected by cell-mediated immunity, even in the absence of antibody response. In conclusion, double-dose mRNA vaccination generated a humoral response in 54% of our CLL cohort, and a third dose induced seroconversion in 40% of the patients who were seronegative after the second dose. However, the strongest boost to the immune response against the virus seems to be the COVID-19 infection, as a substantial increase in anti-Spike antibodies was observed in all CLL patients after infection, even if they were negative post-vaccination.