Immunologic Responses After COVID-19 Vaccination in Patients With Membranous Nephropathy Receiving Anti–CD38 Felzartamab Therapy: Results From the Phase 1b/2a M-PLACE Study
Abstract
Introduction Mass vaccination against SARS-CoV-2 has been one of the pivotal public health strategies to curb the COVID-19 outbreak. Currently, there are insufficient data on the immune response to COVID-19 vaccines in patients with autoimmune kidney diseases, especially those receiving immunosuppressive drugs. Patients who are immunocompromised are at a higher risk of a severe disease course if infected with SARS-CoV-2 and are less likely to mount an adequate immune response to vaccination.S1 Primary membranous nephropathy (MN) is an autoimmune kidney disease and a leading cause of nephrotic syndrome in adults worldwide.S2 Approximately 75% of primary MN cases arise because of autoantibodies that target the phospholipase A2 receptor (PLA2R) on podocytes.S2 High titers of anti-PLA2R autoantibodies have been associated with more severe disease courses and a longer time to achieve remission.S3 The probable source of anti–PLA2R antibodies is CD38 high-expressing plasmablasts and plasma cells.S4,S5 Depleting B cells (plasma cell precursors) has been recognized as a promising therapeutic strategy for autoimmune diseases, with a number of agents currently under development or approved for clinical use.S4,S6 However, these treatments have been associated with impaired humoral response after COVID-19 vaccination.1,S7 Felzartamab (MOR202), an investigational, fully human IgG1 anti-CD38 monoclonal antibody that depletes plasmablasts and plasma cells via antibody-dependent cell-mediated cytotoxicity and antibody-dependent cell-mediated phagocytosis, is currently being evaluated for the treatment of anti-PLA2R antibody-positive MN.2,S8 To elucidate whether the plasma cell-depleting effect of felzartamab precludes response to vaccination against SARS-CoV-2, the Roche Elecsys anti-SARS-CoV-2 S assay was used to investigate the humoral immune responses of COVID-19 vaccines in patients with anti-PLA2R antibody-positive MN treated with felzartamab in the ongoing phase 1b/2a M-PLACE study (NCT04145440)2 (Supplementary Methods). Results Of the 31 patients enrolled in the M-PLACE study, 19 (61.3%) were vaccinated against SARS-CoV-2. Among these patients, the median age was 63 years, 73.7% received at least 2 doses of a COVID-19 vaccine, the majority (68.4%) were vaccinated with the Pfizer-BioNTech vaccine, and 47.4% received their first vaccination after initiation of felzartamab treatment (Table 1, Supplementary Figure S1, and Supplementary Table S1).