Serological Response after Two Doses of Sars-Cov-2 Vaccines in CML Patients - a Prospective Study of a Brazilian Center

Abstract

COVID-19 is associated with a worse prognosis in patients with hematologic malignancies. The mortality rate of CML patients with COVID-19 was 5,5 - 13% before COVID-19 vaccination was available. There are few studies about the efficacy of SARS-CoV-2 vaccines in this population. Objectives This study aimed to evaluate the seroconversion rates after two doses of SARS-CoV-2 vaccines in chronic myeloid leukemia (CML) patients who were receiving tyrosine kinase inhibitors (TKIs) or in treatment-free-remission (TFR). Methods Peripheral blood samples were collected from CML patients 1 to 3 months after two doses of SARS-CoV-2 vaccines to perform a qualitative screening serologic test (CMIA, SARS-CoV-2 IgM, IgG - Alinity System, Abbott Laboratories, Ireland). Samples from the reactive tests underwent a second analysis through quantitative IgG (anti-S1) assessment (SARS-CoV-2 IgG II Quant, Alinity System, Abbott Laboratories, Ireland) and for neutralizing antibody titers (nAbs), which detects the cytopathic effect of the virus in culture (Vero CCL-81 cells) elicited by the vaccines. Results Between August and November 2021, 102 CML patients were evaluated. The median age was 56,2 years (33-85), 58,8% were male, and 40,2% had at least one comorbidity. 98% of the patients were in the chronic phase (CP), and 80% had at least a major molecular response (MMR); 87% received TKI, and 13% were in treatment-free remission (TFR). Among 102 patients, 66,7% received ChAdOx1 nCoV-19 (AZD1222)-Covishield (Oxford/AstraZeneca/Fiocruz) vaccine, 29,41% CoronaVac (Sinovac/Butatan) vaccine, 1,96% BNT162b2 (Pfeizer/BioNTech/Fosun Pharma) vaccine and 1,96% Ad26.COV2.S (Janssen-Cilag) COVID-19 vaccine. Fifteen % had mild COVID-19 before vaccination. A screening qualitative serologic test (CMIA) was positive in 26/102 (25%) patients. COVID-19 before vaccination was associated with IgG antibody positivity (p<=0.001). nAbs titers were higher than 1:320 in 13/26 cases; 5 had COVID-19 before completing the vaccination scheme. Patients received ChAdOx1 nCoV-19 vaccine (76%), Coronavac (19%) and BNT162b2 (1%). There were 7 COVID-19 confirmed cases and two suspected. Eight cases occurred before vaccination, and one presented a mild COVID-19 after ChAdOx1 nCoV-19's first dose. Eleven were treated with imatinib (first line), six patients with dasatinib and one with nilotinib (second-line, 6 with MMR), 5 in third or fourth line (no MMR) and three patients were in TFR. The proportion of patients with nAbs > 1:320 was superior in the group receiving a third or fourth line (p=0.022). Seroconversion rates (CMIA, IgM and IgG) between CoronaVac and ChAdOx1 nCoV-19 were not statistically significant. There was no difference in seroconversion rates according to the patient's age or in those treated with TKI or in TFR (p=0.77). Conclusions In the present study, the serological response of CML patients after two vaccine doses was lower than observed in the general population, reinforcing the importance of the third dose. No differences were identified between the vaccine type (Coronavac vs. ChAdOx1 nCoV-19). nAbs titers were higher in the group treated in the third or fourth line. However, this group had more patients with COVID-19 prior to vaccination. Therefore, further studies are necessary to evaluate if TKI treatment could interfere with the vaccine's efficacy.