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Objective: To describe determinants of persisting humoral and cellular immune response to the second COVID‐19 vaccination among patients with myeloma. Methods: This is a prospective, observational study utilising the RUDYstudy.org platform. Participants reported their second and third COVID‐19 vaccination dates. Myeloma patients had an Anti‐S antibody level sample taken at least 21 days after their second vaccination and a repeat sample before their third vaccination. Results: 60 patients provided samples at least 3 weeks (median 57.5 days) after their second vaccination and before their third vaccination (median 176.0 days after second vaccine dose). Low Anti‐S antibody levels (<50 IU/mL) doubled during this interval (p =.023) and, in the 47 participants with T‐spot data, there was a 25% increase negative T‐spot tests (p =.008). Low anti–S antibody levels prior to the third vaccination were predicted by lower Anti‐S antibody level and negative T‐spot status after the second vaccine. Independent determinants of a negative T‐spot included increasing age, previous COVID infection, high CD4 count and lower percentage change in Anti‐S antibody levels. Conclusions: Negative T‐spot results predict low Anti‐S antibody levels (<50 IU/mL) following a second COVID‐19 vaccination and a number of biomarkers predict T cell responses in myeloma patients. [ABSTRACT FROM AUTHOR]

Summary: 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 the 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 three 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. In all, 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 (B‐cell maturation antigen) therapy and Pfizer‐BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination. [ABSTRACT FROM AUTHOR]