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. 2024 Jun 18;6(8):100853.
doi: 10.1016/j.xkme.2024.100853. eCollection 2024 Aug.

Obinutuzumab in Refractory Membranous Nephropathy: A Case Series

Yuxin Lin  1 , Quan Han  1 , Liangliang Chen  1 , Yaomin Wang  1 , Pingping Ren  1 , Guangjun Liu  1 , Lan Lan  1 , Xin Lei  1 , Jianghua Chen  1 , Fei Han  1
Affiliations

Obinutuzumab in Refractory Membranous Nephropathy: A Case Series

Yuxin Lin et al. Kidney Med. .

Abstract

Rationale & objective: Membranous nephropathy (MN), recognized as an autoimmune kidney disease, responds well to anti-CD20 monoclonal antibodies. Obinutuzumab, a type Ⅱ humanized anti-CD20 and immunoglobulin G1 Fc-optimized monoclonal antibody, when compared with rituximab, has demonstrated superior efficacy in B-cell leukemia and lymphoma, especially in rituximab-resistant cases. However, the efficacy and safety of obinutuzumab in MN remain unclear.

Study design: A case series study.

Setting & participants: A total of 18 patients were diagnosed with MN and had received obinutuzumab at our center without secondary MN, undergoing dialysis, having a history of kidney transplantation, or infections requiring treatment.

Exposure: Obinutuzumab treatment.

Outcomes: Primary outcomes included remission rate, time to first remission, and first relapse-free survival time during the follow-up period.

Analytical approach: Survival analysis was performed with Cox proportional hazards models, log-rank test, and Kaplan-Meier survival analysis.

Results: Patients with MN (median age of 52.5 years, 83.3% males) received an average dose of 2.1 ± 0.8 g of obinutuzumab during a median follow-up period of 13.6 months. During the follow-up, 17 patients (94.4%) achieved remission, with 12 patients (66.7%) achieving partial remission, and 5 patients (27.8%) achieving complete remission. The median time to first remission and first relapse-free survival time was 2.7 (1.0-6.1) months and 9.8 (2.6-11.2) months, respectively. Of 12 patients with previous rituximab treatment, all achieved remission successfully, with 8 (66.7%) achieving partial remission and 4 (33.3%) achieving complete remission. Adverse events were mostly mild, and no severe treatment-related adverse events were observed.

Limitations: Limited or missing data; risks of selection bias; or recall bias; underestimated first relapse-free survival time because of a limited follow-up period; unmonitored counts of CD19+ B-cells and other lymphocyte subsets.

Conclusions: Obinutuzumab demonstrated promising efficacy and safety in inducing remission in MN, particularly in patients with an unsatisfactory response to rituximab.

Keywords: Obinutuzumab; membranous nephropathy; remission; rituximab.

Plain language summary

Membranous nephropathy (MN), an autoimmune kidney disease, usually responds favorably to rituximab, a chimeric anti-CD20 monoclonal antibody. Nevertheless, certain patients exhibit inadequate responses to rituximab. Obinutuzumab, a novel humanized anti-CD20 monoclonal antibody, has shown enhanced efficacy in cases where rituximab fails to address B-cell leukemias and lymphomas. However, its efficacy and safety in MN treatment remain uncertain. A case series involving 18 patients treated with obinutuzumab at our center demonstrated promising results, suggesting favorable efficacy and safety in inducing and maintaining remission, particularly among patients who did not respond well to rituximab previously. These findings signify a potential alternative for MN treatment, though further research is needed to confirm them.

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Figures

Figure 1
Figure 1
(A) Probability of achieving remission (either partial remission or complete remission) after obinutuzumab in all patients (n = 18). (B) Probability of achieving remission after obinutuzumab in PLA2R subgroups. “PLA2R-associated” (n = 15) was defined as either serum anti-PLA2R antibody titers exceeding 50 RU/mL or positive immunofluorescence staining for PLA2R antigen on kidney biopsy. (C) Probability of achieving remission after obinutuzumab in previous-rituximab subgroups. “With previous rituximab” (n = 12) was defined as having received at least 1 course of rituximab before the initial infusion of obinutuzumab.
Figure 2
Figure 2
(A) Change of urine protein creatinine ratio (uPCR) after obinutuzumab in all patients (n = 18). (B) Change of uPCR after obinutuzumab in PLA2R subgroups. “PLA2R-associated” (n = 15) was defined as either serum anti-PLA2R antibody titers exceeding 50 RU/mL or positive immunofluorescence staining for PLA2R antigen on kidney biopsy. (C) Change of uPCR after obinutuzumab in previous-rituximab subgroups. “With previous rituximab” (n = 12) was defined as having received at least one course of rituximab before the initial infusion of obinutuzumab.
Figure 3
Figure 3
(A) Change of serum albumin level after obinutuzumab in all patients (n = 18). (B) Change of serum albumin level after obinutuzumab in PLA2R subgroups. “PLA2R-associated” (n = 15) was defined as either serum anti-PLA2R antibody titers exceeding 50 RU/mL or positive immunofluorescence staining for PLA2R antigen on kidney biopsy. (C) Change of serum albumin level after obinutuzumab in previous-rituximab subgroups. “With previous rituximab” (n = 12) was defined as having received at least 1 course of rituximab before the initial infusion of obinutuzumab.
Figure 4
Figure 4
(A) Change of serum creatinine level after obinutuzumab in all patients (n = 18). (B) Change of serum creatinine level after obinutuzumab in PLA2R subgroups. “PLA2R-associated” (n = 15) was defined as either serum anti-PLA2R antibody titers exceeding 50 RU/mL or positive immunofluorescence staining for PLA2R antigen on kidney biopsy. (C) Change of serum creatinine level after obinutuzumab in previous-rituximab subgroups. “With previous rituximab” (n = 12) was defined as having received at least 1 course of rituximab before the initial infusion of obinutuzumab.
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