Prospective study of immunogenicity to SARS-CoV-2 booster vaccines in multiple myeloma and Waldenström macroglobulinemia.

Patients with multiple myeloma (MM) and Waldenström macroglobulinemia (WM) have increased risk of severe coronavirus disease 2019. Impaired humoral responses to the primary vaccination series against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in patients with MM and WM, but the impact of booster vaccinations and functional status of the elicited antibodies are unknown. We performed a prospective cohort study investigating SARS-CoV-2 vaccination in patients with MM (n = 93) and WM (n = 48). The primary end point was effective immune response (EIR) at 28 days after the primary vaccination series (ie, anti-spike SARS-CoV-2 antibody titer >250 U/mL). The EIR rate after the primary vaccination series was 47% and 25% in patients with MM and WM, respectively. After the first and second booster vaccinations, the EIR rates increased to 84% and 91% in patients with MM and 60% and 89% in those with WM, respectively. Factors associated with lower EIR in patients with MM were hypogammaglobulinemia, lymphopenia, and treatment with anti-CD38 monoclonal antibody or corticosteroid. In patients with WM, treatment with a Bruton tyrosine kinase inhibitor or rituximab was associated with a lower EIR, whereas asymptomatic and treatment-naïve patients had a higher EIR. Functional profiling identified reduced antibody-dependent cellular phagocytosis, neutrophil phagocytosis, and natural killer cell activity against wild-type and variant SARS-CoV-2 (Alpha, Beta, and Gamma) in patients with MM and WM compared to healthy donors. Our data demonstrate that although patients with MM and WM have impaired humoral responses to the primary SARS-CoV-2 vaccination series, repeated booster vaccines significantly improve immunogenicity. This trial was registered at www.ClinicalTrials.gov as #NCT04830046.