Vaccination Against SARS-CoV-2 for Myeloma Patients: Do We Need a Booster Dose and How Frequent?

Abstract

Patients with multiple myeloma (MM) are at increased risk for severe COVID-19 disease, hospitalization and death. In this context, it is essential to maintain an adequate immune profile. A third (first booster) dose has been offered with priority to patients with MM due to their immunocompromised status and the suboptimal immune response to the initial vaccination schedule against COVID-19. Three important studies that investigate the immune profile following a booster vaccination with a mRNA-based vaccine have been recently published.The first study was published in Blood (2022;139(9):1409-1412) by Terpos et al and included 167 consecutive patients with MM who were vaccinated with the booster BNT162b2. All patients had been fully vaccinated with the 2-dose BNT162b2. Median time between the second and the booster dose was less than 5 months. The booster dose significantly improved the median neutralizing antibody (NAb) response in patients with MM (27.1% before to 96.7% after the third dose p<0.001). Importantly, almost half of the patients with suboptimal NAb responses at one month after the second dose of BNT162b2 developed NAb titers of at least 50% at one month after the booster dose. Treatment with anti-BCMA agents emerged as a significant adverse predictive factor for NAb response to the booster shot. None of these patients achieved a NAb level above the positivity threshold.The second study was published in Cancer Cell (2022;40(5):441-443) by Aleman et al and included 261 patients with MM with available anti-SARS-CoV-2 spike (S) IgG measurements at least 1 week after the third vaccine shot. Anti-S IgG levels increased significantly after administration of the third dose both in patients with and without prior history of COVID-19 (p<0.001), although the depth of humoral response was inferior to healthy individuals. Importantly, 60 out of 68 seronegative patients before the third dose seroconverted with the booster shot. Neutralizing titers against the Omicron variant after the booster dose were detectable in only 54% of MM patients who responded to two doses of the vaccine (they had adequate protection against Wuhan variant) and in none of those who did not respond in the initial vaccine doses. The third vaccine shot significantly increased spike-specific CD4+ T cell-mediated cytokine responses, as well.The third study was published in Cancer Cell again (2022;40(6):587-589) by Enssle et al and included 71 patients with MM and 23 healthy controls. The authors observed a 4-fold increase in anti-S IgG levels from a median of 193.2 BAU/ml before to 776.0 BAU/ml after the booster dose in the MM cohort. However, a poor neutralization capacity against the Omicron variant was observed. Regarding cellular immunity, MM patients showed a significant T-cell response against the wild-type virus, the Delta variant and the Omicron variant, although the response was attenuated in the latter case.Overall, the abovementioned studies advocate for prioritizing patients with MM, especially those on anti-BCMA treatments, for additional booster shots, ideally with variant-adapted vaccines, or with the prophylactic administration of monoclonal antibodies against SARS-CoV-2. The standard vaccine seems not to prevent the infection with omicron variant(s) and thus general preventive measures including mask wearing and avoiding crowds remain important for these vulnerable patients.