Long-Term Immune Response to SARS-CoV-2 Vaccination in Hematologic Malignancies: An Update of the ImV-HOng Trial of the East German Study Group for Hematology and Oncology

<b>Purpose</b>: Evaluate long-term immunogenicity and its association with the number of vaccines and breakthrough infections in patients with hematologic malignancies compared to a healthy cohort. <b>Methods</b>: This study is an amendment of a multicenter study (DRKS00027372) which described the upsurge of anti-spike-IgGs on day 120 from a blunted day-35 response in patients with hematologic neoplasms. In this amendment, 191 individuals from the original study (patients with myeloid and lymphoid neoplasms and controls) were followed beyond month 12 after first SARS-CoV-2-vaccination. The long-term humoral and cellular responses and their correlation with the number of vaccines were studied. <b>Results</b>: After a median follow-up of 18 months, a median of three vaccinations (range 1-5) were given. Antibody levels did not correlate with the number of vaccinations (≤2 versus ≥3) (<i>p</i> = 0.3). With a median of 5274 U/mL anti-spike-IgGs, the inferior day-120 antibody response in patients with lymphoid neoplasms was no longer detected. Breakthrough SARS-CoV-2-infections, mostly mild, occurred in 67% of controls and 46% of patients. Patients with lymphoid neoplasms with two vaccinations did not have more infections compared to patients with more doses (<i>p</i> = 0.4). There was a significant decline in the spike-specific T-cell response for CovCD4⁺ and CovCD8⁺ (<i>p</i> < 0.001). On last assessment, 33% of individuals lost their day-120 CovCD4⁺-positive response (<i>p</i> < 0.001). There was no correlation between the number of vaccinations and cellular immune response in patients and controls (<i>p</i> = 0.3). <b>Conclusions</b>: In this study, breakthrough infections were high despite repeated boosting, which by itself does not lead to an upsurge in the cellular immune response in the majority of patients.