Analysis of Immunological and Clinical Response to Vaccination Against Sars-COV-2 in Patients with Chronic Myeloid Leukemia

Background: Patients with oncohematological malignancies have been excluded from the clinical trials in which the vaccines against COVID-19 were approved. Although there are some studies that have evaluated the immunologic and clinical response to SARS-CoV-2 in patients with different oncohematologic diseases, the response developed by patients with Chronic Myeloid Leukemia (CML) has been little explored.

Objective: To evaluate the immune and clinical response to vaccination against SARS-CoV-2 in patients with CML.

Materials and methods: We prospectively studied the humoral and cellular immune response to SARS-CoV-2 before and 1 month after receiving two doses of a COVID-19 mRNA vaccine in CML patients (n=29) compared to healthy donors (n=24). Among the CML patients, 5/29 (17%) had not received active treatment with tyrosine kinase inhibitors in the previous 12 months. Direct cellular cytotoxicity (DCC) studies of peripheral blood cells (PBMCs) against pseudotyped SARS-CoV-2 infec- ted Vero E6 cells were performed by measuring Caspase-3 activation and cytotoxic populations were phenotyped by flow cytometry. Antibody-dependent cell-mediated cytotoxicity (ADCC) analysis was performed using Raji cells as the target of PBMCs and quantifying apoptosis induction by measuring the levels of Annexin V.

Results: 1) CML patients presented an early humoral response against COVID-19 similar to healthy donors, with a 5-fold increase over baseline values (p<0.0001). 2) No differences in neutralizing antibody titers against SARS-CoV-2 were observed between CML patients and healthy donors. 3) CCDA studies showed similar responses between CML patients and healthy donors, with no increase in this response after 1 month receiving two doses of the vaccine (Figure 1A). 4) CCD studies showed higher baseline activity in PBMCs from CML patients, probably due to immunomodulatory treatment or the disease itself, although the results did not reach statistic significance (Figure 1B), these results being maintained independently of the populations studied (CD8; NK (CD3-CD56+); CD3+CD8±TCRgd+). 5) No significant differences were observed between the response developed by patients with CML on active treatment compared to those in the treatment-free phase. 6) A total of 10 breakthrough infections were observed in vaccinated patients, all of which were mild.

Conclusions: The results of this study show that the humoral and cellular immune response developed after vaccination against COVID-19 is not compromised in patients with CML. Similarly, treatment with tyrosine kinase inhibitors does not seem to affect the immune response.

This work was supported by the Strategic Action in Health 2017-2020 of the Instituto de Salud Carlos III (PI21/00877).

No relevant conflicts of interest to declare.