Impaired acute-phase humoral immunity is the major factor predicting unfavorable outcomes in multiple myeloma patients with SARS-CoV-2 Omicron variants outbreak infection.

At the end of 2022, a huge tide of SARS-CoV-2 infection mainly Omicron BA.4/5 developed in China. Multiple myeloma (MM) patients suffered cancer deterioration and mortality from COVID-19, yet profound analyses of Omicron variants-induced immunity function are scarce. We presented a longitudinal study in 218 MM patients and 73 healthy controls (HCs), reporting the prognostic factors and dynamic humoral and cellular immune responses. Neutralizing antibody and interferon γ ELISpot assay of SARS-CoV-2 was tested at three time points: 2-4, 8-10, and 14-16 weeks after infections. Our data showed older age, active MM, relapsed/refractory MM (R/RMM), immunotherapy, comorbidity, and non-vaccination were risk factors associated with hospitalization. Severe humoral immunity impairment within 2-4 weeks was especially seen in patients with unvaccinated, older age, immunotherapy, R/RMM and comorbidities, while T-cell response was relatively intact. Although antibodies of Omicron variants reached positive levels in MM patients at 8-10 weeks, half lost effective antibody protection at 14-16 weeks. However, most seronegative patients (76.2% at 2-4 weeks, 83.3% at 8-10 weeks) could develop effective T-cell response. Notably, the inactivated wild-type vaccinated patients exhibited weaker humoral and cellular immunity only at 2-4 weeks, escalating to similar levels as those in HCs later. Our findings indicate impairment of humoral immunity at acute-phase after infection is the major factor correlated with hospitalization. One-month suspension of immune therapy is suggested to prevent serious infection. These results confirm the value of inactivated vaccine, but indicate the need for additional booster at 14-16 weeks after infection for high-risk MM population.