P-127: Patients with Multiple Myeloma on treatment with Anti-CD38 or Anti-BCMA agents have a suboptimal humoral response following COVID-19 vaccination

Abstract

BackgroundRecent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies, especially under immunosuppressive therapy. Herein, we evaluated the development of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with plasma cell neoplasms after vaccination with either the mRNA BNT162b2 or viral vector AZD1222 vaccine.MethodsSerum of both patients and controls was collected on day 1 (D1; before the first BNT162b2 or AZD1222 dose), on day 22 (D22; before the second dose of the BNT162b2 or 3 weeks post the first AZD1222 dose) and on day 50 (D50; 4 weeks post second dose of the BNT162b2 or 7 weeks post the first AZD1222 dose). NAbs against SARS-CoV-2 were measured using FDA approved-ELISA methodology.ResultsPatients with MM (n=213), SMM (n=38) and MGUS (n=25) and 226 healthy controls, of similar age and gender, were enrolled in the study (NCT04743388). Two hundred and fifteen patients (77.9%) were vaccinated with the BNT162b2 and 61 (22.1%) with the AZD1222 vaccine. Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine leads to lower production of NAbs against SARS-CoV-2 in patients compared with controls both on day 22 and on day 50 (P<0.001 for all comparisons). After the first dose of the vaccine, on D22, the median NAb inhibition titer was 27% (IQR: 15.3-42%) for patients versus 38.7% (IQR: 22-54.3%) for controls (P<0.001). On D50, the median NAb inhibition titer was 62.8% (IQR: 26-88.9%) for patients versus 90% (IQR: 58-96.4%) for controls (P<0.001). The respective number of patients and controls who developed NAb titers ≥50% (clinically relevant titers) was 158 (57.3%) and 183 (81%), respectively (P<0.001). Furthermore, MM patients showed an inferior NAb response compared with MGUS on day 22 (p=0.009) and on day 50 (p=0.003); MGUS patients’ NAb development was similar to controls. Importantly, active treatment with either anti-CD38 monoclonal antibodies or belantamab mafodotin and lymphopenia at the time of vaccination were independent prognostic factors for suboptimal antibody response following vaccination (OR: 9.4, 95% CI: 1.7-51.1, p=0.009, OR 2.9, 95% CI: 1.2-7.1, p=0.002 and OR: 3.5, 95% CI: 1.8-6.7, p=0.019, respectively). Seventy-one (33%) and 68 patients (31.6%) reported mild reactions after the first and second dose of the BNT162b2 vaccine, respectively. Twenty (32.8%) patients vaccinated with the first dose of AZD1222 also presented with local reactions.ConclusionIn conclusion, MM patients have lower humoral response following SARS-CoV-2 vaccination compared to gender- and age-matched controls. Treatment with anti-CD38 and belamaf-based regimens as well as lymphopenia at the time of vaccination independently predicted for poor NAb development. These data underline the need for timely vaccination, ideally during a treatment-free period, and for continuous vigilance on infection control measures.