ABSTRACT
Introduction: Patients with hematological malignancies have a higher susceptibility to develop severe COVID-19 and their humoral response to vaccination is usually impaired due to the immunosuppression caused by treatments or the disease itself. A recent prospective study that analyzed the humoral response to the BNT162b messenger RNA (mRNA) COVID-19 vaccine in patients with CLL showed an antibody response rate of 39.5%, significantly lower than that of sex- and agematched healthy controls. Patients with active disease or under treatment, especially with targeted agents were the ones with the worst humoral response (Herinashu et al., 2021). More data are needed to validate these results and enhance protective strategies in those patients. In this study, we aimed to assess the humoral response following vaccination with the mRNA SARS-CoV-2 vaccine in a cohort of CLL patients from routine clinical practice and compared it with patients with other hematological neoplasms. Methods: Twenty-two CLL patients underwent blood sampling 2-4 weeks after the second dose of BNT162b2 (Pfizer- BioNTech) or mRNA-1273 (Moderna) vaccine. A control group was composed of 65 patients with other hematological cancers that also received mRNA vaccines. IgG antibodies against SARS-CoV-2 Spike antigen were measured using electrochemiluminescent assay (ADVIA Centaur XPT, Siemens), and responses reported as index inferior or superior to 1 (range 0.50-150.00), being index <1.00 informed as no reactive and index >1.00 as reactive. Statistical analyses were performed using SPSS, version 22.0 (IBM SPSS Statistics, IBM Corporation). Results: CLL patient's characteristics are shown in Table 1. Antibody-response to the vaccine was only obtained in 54.5% of the patients with CLL (12/22) and was significantly lower than that observed in the control group, in which 77.8% of the patients with other malignancies seroconverted (p=0.03), Figure 1. The other malignancies group was composed of multiple myeloma (N=21);indolent non-Hodgkin lymphoma (NHL) (N=12), Hodgkin lymphoma (N=5);acute myeloblastic leukemia (N=1);myeloproliferative neoplasms (N=12);myelodysplastic syndromes (N=7) and aggressive NHL (N=7). Antibody titers in patients with CLL showed a trend to be lower than the control group [median 3.16 (0-150) vs. 52.95 (0-150), p=0.133]. Focusing on CLL patients, antibody response rate was higher when disease was not active (75 vs. 43%, p=0.1) and in treatment-naïve patients (66.7 vs. 52.6%, p=0.6). Moreover, we observed similar responses in patients who obtained clinical remission after treatment (56.6 vs. 50%, p=0.8%). In patients under treatment with targeted drugs (Bruton's tyrosine kinase inhibitors (BTKi) or venetoclax based regimens) at the time of vaccination, antibody response rates were significantly lower (33 vs. 80%, p=0.03). Specifically, 40% of patients under BTKi showed a serologic response, and only 25% of patients under venetoclax-based regimens. Of note, at the moment of the study, the disease was controlled in all patients under continuous treatment. Conclusions: Antibody-mediated response to mRNA COVID-19 vaccines in CLL patients is significantly impaired in comparison to other onco-hematological diseases. Our series confirms better response rates when the disease is controlled and in treatment-naïve patients, showing slightly better responses than published to date (54.5 vs. 39.5%), which reinforces the need to vaccine CLL patients as some of them will benefit. Special concern must be taken to patients treated with targeted drugs, who show very low humoral responses. Therefore, in this vulnerable population, preventive measures, such as masks wearing, social distancing, and co-habitants vaccination should be reinforced.