Immune response to COVID-19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T cell response.

Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID-19 vaccination. Using a prospective study of myeloma patients in UK Rudy Study cohort, we assessed humoral and Interferon gamma release assay (IGRA) cellular immune responses to COVID-19 vaccination post second COVID-19 vaccine administration. We report data from 214 adults with myeloma (n=204) or smouldering myeloma (n=10) who provided blood samples at least 3 weeks after second vaccine dose. Positive Anti-Spike antibody levels (> 50 IU/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative Anti-Spike protein antibody response. 95/158 (60.1%) patients produced positive results for both anti-Spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti-CD38/ anti-BCMA therapy and Pfizer-BioNTech (PB) vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination.