P-398: Dynamic immune response in multiple myeloma patients infected with SARS-CoV-2 Omicron BA.4/5 subvariant in China

Introduction: Patients with multiple myeloma (MM) experienced a high risk of severe disease and mortality during the SARS-CoV-2 pandemic for compromised immunity. However, the immunological characteristics in MM patients with Omicron BA.4/5 subvariant infection remained largely unclear. At the end of 2022, a huge tide of SARS-CoV-2 infection mainly Omicron BA.4/5 developed in China. This study aims to illustrate the dynamic immune response in MM patients after infection to better guide the treatment and vaccination.

Methods: All MM patients and age- and sex-matched healthy controls (HCs) were recruited from Peking Union Medical College Hospital. Risk factors for COVID-19 infection or hospitalization were analyzed using logistic regression. The titers of neutralizing antibodies toward BA.4/5 subvariant were measured monthly since infection and presented as the inhibition rate (%).

Results: In total, 218 MM patients (80.7% infected) and 73 infected HCs were enrolled and followed up for 3 months. Of the 176 infected MM patients, 83 (47.2%) were vaccinated, while only 5 (23.8%) of 21 hospitalized patients fulfilling the criteria of severe COVID-19 were vaccinated. Neither univariate nor multivariate analyses identified risk factors associated with infection. Nevertheless, older age, active MM, relapsed/refractory MM (R/RMM), immunotherapy, comorbidity, and non-vaccination were risk factors associated with hospitalization. Older age and immunotherapy were independent risk factors. Compared with HCs and vaccinated patients, unvaccinated MM patients showed significantly lower neutralizing antibody inhibition rates at all 3 time-points. Vaccinated MM patients also exhibited weaker titer of neutralizing antibodies only at the first month while escalating to a similar level as those in HCs later. In MM patients, the maximum antibody level was detected at 2 months. Notably, only 48% unvaccinated MM patients were able to maintain protective antibody levels at 3 months. Moreover, 12/21 (57.1%) hospitalized patients could not develop effective protective antibodies within 1 month after infection. Nineteen (52.8%) over 36 patients receiving immunotherapy also failed to produce sufficient antibodies in the early stages. After one-month break of anti-myeloma therapy, the antibody titer climbed to a similar level as that in patients without immunotherapy.

Conclusions: Within the first month, MM patients with older age, R/RMM, immunotherapy, comorbidity, and non-vaccination are associated with hospitalization for compromised humoral immunity. Although most MM patients reached the peak of protective antibody at 2 months, high-risk sub-population such as those unvaccinated or older than 65 will be at risk of a second infection after 3 months. The inactivated wild-type vaccine remains effective against the BA.4/5 subvariant in MM patients. Therefore, extra-shots of inactivated SARS-CoV-2 are suggested for high-risk MM patients 3 months after the first infection.