Monthly Mini-Dose Rituximab for Primary Membranous Nephropathy: A Different Approach

Abstract

Background: The currently recommended dose of rituximab for primary membranous nephropathy is as high as that for lymphoma.This study assessed the efficacy of monthly 100 mg rituximab monotherapy in patients with primary membranous nephropathy.
Methods: This retrospective study included 32 patients with primary membranous nephropathy treated at Peking University Third Hospital between March 2019 and January 2023.All patients were anti-phospholipase A2 receptor (PLA2R) antibody-positive and received rituximab 100 mg intravenously monthly for at least 3 months without other immunosuppressive therapy.
Conclusions: Monthly rituximab 100 mg appeared as a potential effective regimen for treating anti-PLA2R-associated primary membranous nephropathy with a low anti-PLA2R titer.
Figure 2. clinical data between different anti-PLA2R titer groups before and after monthly mini-dose rituximab treatment.Background: Felzartamab (felza) is a fully human monoclonal antibody that binds to CD38 with high affinity and depletes CD38+ antibody-producing cells such as plasma cells/plasmablasts primarily via antibody-dependent cellular cytotoxicity & phagocytosis.

SA-PO910
In studies of high-risk PMN patients, felza substantially reduced aPLA2R with associated improvements in UPCR and serum albumin.To further characterize felza with respect to efficacy biomarkers and preservation of protective immunity, we analyzed samples collected prospectively during the M-PLACE (NCT04145440) and NewPLACE (NCT04733040) trials.
Results: Felza reduced aPLA2R comparably in patients with baseline levels <150 and ≥150 RU/mL (Table 1).A dose-dependent effect on aPLA2R reduction at 6 months was observed across both M-PLACE (9 infusions) and NewPLACE (5 or 2 infusions).Depletion of detectable CD38+ plasmablasts was observed 1 wk after felza treatment.Treatment did not impact other B cell populations, as absolute counts of total, naïve, and memory B cells were unchanged.Total IgG decreased on treatment then recovered above baseline by end of study.Anti-TT titers decreased on treatment, however levels were maintained above the protective threshold (0.1 IU/mL).
Conclusions: Felza selectively depleted CD38+ plasmablasts and plasma cells, reducing pathogenic aPLA2R to a greater extent than protective anti-TT titers and total IgG, which was dose-dependent and durable.Treatment of PMN with Felza suggests an efficient and selective treatment concept with preservation of vaccine response compared to conventional immunosuppressive therapies.
Methods: We analysed data of incident patients with MN, at high risk for progression, treated according the prescribed protocol.aPLA2Rab levels were measured by ELISA in available samples collected at baseline (n=26), and 2 (n=18), 4 (n=20), 8 (n=20) and 12 (n=23) weeks after start of therapy.
Conclusions: Our study showed early and high immunological response rate in patients with PLA2Rab associated MN.The longer T1/2 in patients with very high PLA2Rab levels suggest immunological differences (increased B cell proliferation, presence of long-lived plasmacells).Assessment of PLA2Rab levels within 2-4 weeks after start of therapy may enable to identify patients who need more intensive therapy.

Analysis of the Efficacy and Influencing Factors of Rituximab in the Treatment of Primary Membranous Nephropathy
Jiawei Cheng, Zhangzhe Peng.Xiangya Hospital Central South University, Changsha, China.
Background: Membrane nephropathy (MN) is the most common primary glomerular disease that causes adult nephrotic syndrome in the world.Primary membranous nephropathy (pMN) can progress to end-stage renal disease.Rituximab (RTX) has been listed as the first-line treatment for patients with medium and high risk pMN.
Methods: This study retrospectively analyzed 83 patients with pMN in XX Hospital who were confirmed by renal biopsy and received RTX treatment.According to the clinical outcome, the patients were divided into complete remission (CR), partial remission (PR) and no response (NR).CR, PR were considered effective in treatment while NR was considered ineffective in treatment.The baseline values of patients with different clinical outcomes were compared to explore the influencing factors that affect the efficacy of RTX in the treatment of pMN patients.
Results: After a follow-up of 10.66 (7.25, 16.46) months, 65.1% of those pMN patients achieved clinical remission, of which 27.7% had complete remission and 37.3% had partial remission.Patients with effective treatment (CR, PR) showed a significant decrease in urinary protein creatinine ratio after RTX treatment, while creatinine and eGFR remained stable.Patients with ineffective treatment (NR) showed no decrease in urinary protein creatinine ratio after RTX treatment, while creatinine significantly increased and eGFR significantly decreased.During follow-up, 9 patients (10.8%) experienced infection related adverse reactions.Multivariate Cox regression analysis showed that the combined use of glucocorticoids (p=0.027,HR=2.05), serum albumin (p=0.006,HR=1.10), and urinary light chain LAMBDA/KAPPA ratio (>0.622)(p=0.011,HR=0.33) were independent influencing factors on the effectiveness of RTX in treating pMN.Patients with lower serum albumin and higher urinary LAMBDA/KAPPA ratio may be more likely to have ineffective treatment, and the combined use of glucocorticoids may promote RTX induced disease remission.
Conclusions: RTX has a good therapeutic effect on pMN, which can reduce urinary protein and increase albumin in patients, maintain the stability of blood creatinine and eGFR, and have a low incidence of adverse reactions.The combined use of glucocorticoids, serum albumin and urinary LAMBDA/KAPPA ratio are independent factors affecting the effectiveness of RTX in the treatment of pMN.
Funding: Clinical Revenue Support