B08: A THIRD BNT162B2 DOSE INDUCES ANTIBODY RESPONSES AGAINST SARS-COV-2 EVEN IN PREVIOUSLY NON-RESPONDERS WITH MULTIPLE MYELOMA

Introduction: Recent data indicate that COVID-19 vaccination leads to a less intense humoral response in patients with multiple myeloma (MM) primarily in those without prior exposure to SARS-CoV-2, as reflected by a lower production of neutralizing antibodies (NAbs), compared with healthy controls. A third BNT162b2 dose in adults aged 60 years and older was associated with significantly increased IgG titers after 10 to 19 days, with no major adverse toxicity. Methods: In this context, we prospectively evaluated the development of NAbs against SARS-CoV-2 (ELISA, cPass™ SARS-CoV-2 NAbs Detection Kit; GenScript, Piscataway, NJ, USA) in patients with MM at 30 days post vaccination with a third dose of the mRNA BNT162b2 vaccine (NCT04743388). Serum samples were collected on the date of the booster dose (just before vaccination) and 4 weeks after. Results: The study population included 167 consecutive MM patients (58% males; median age: 68 years, IQR: 60-75 years) who were vaccinated with the booster BNT162b2 dose between September/October 2021, at the same vaccination center. All patients had been fully vaccinated with the two-dose BNT162b2. At the time of vaccination, the vast majority (93.4%) of patients were receiving anti-myeloma treatment. The booster dose significantly improved the humoral response in MM patients. More specifically, the median (IQR) of NAbs titer reached 96.7% (52.6-97.8%) as compared with 27.1% (13.9%-65.8%) before the third dose (p<0.001). Overall, 114 (68%) patients had less than 50% NAb activity before the third dose. Among them, 75 (65.8%) patients increased their NAb titer to at least 50% after the third dose. Interestingly, the patients who had achieved a NAbs titer of ≥50% at one month after the second vaccine dose were more likely to achieve a NAbs titer of ≥50% at one month after the third dose, as compared with those who had inferior antibody responses after the second dose (p=0.001). Fifty-seven (34%) patients had not developed a sufficient humoral response following the second vaccination (NAbs titer <30%). All of them presented with low NAbs titers before the third dose (median 14.5% (IQR 7.2%-23.3%)). The third vaccine dose boosted the median antibody response to 38.8% (IQR 15.6%-92.3%, p<0.001). At one month after the booster dose, 32/57 (56%) patients showed a NAbs titer above the positivity threshold (≥30%) and 26/57 (45.6%) showed a NAbs titer of ≥50%. In the multivariate analysis, only the presence of a NAbs titer ≥30% at one month after the second dose (Odds Ratio (OR) 9.5, 95% Confidence Interval (CI): 3.3-27.6) and the treatment with anti-BCMA agents (OR 0.03, 95%CI: 0.003-0.27) emerged as significant predictive factors for a NAb titer ≥50% at one month following the third dose. None of patients who were under anti-BCMA therapy achieved a NAbs titer of ≥30% one month after the booster dose. Conclusion: Our study demonstrated that a third BNT162b2 dose in patients with MM optimized the humoral response against SARS-CoV-2, as depicted by the significant increase in NAbs at one month post the booster dose. Importantly, ~46% of patients with suboptimal NAbs responses at one month following the two-dose BNT162b2 vaccination showed NAbs titers over 50% at one month after the booster dose. Taking also into consideration the defective immunity in patients with MM and the current COVID-19 outbreaks, self-protection measures, such as mask wearing and social distancing, remain particularly important.