#1974 Obinutuzumab alone may be an effective option for the initial therapy of adult minimal change disease

Abstract Background and Aims Anti-CD20 monoclonal antibody (such as rituximab) has proven effective and safe in pediatric and adult minimal change disease (MCD) in recent studies. Obinutuzumab, a novel type II humanized anti-CD20 monoclonal antibody, has demonstrated superior efficacy in inducing faster and more sustained B-cell depletion compared to equivalent doses of rituximab. Whether obinutuzumab alone could be used as initial therapy of MCD remains uncertain. We aimed to explore the efficacy and safety of obinutuzumab alone as the initial treatment for adult MCD patients. Method A retrospective study was conducted at Peking University Third Hospital between January 1, 2020 and December 31, 2024, and included adult patients with MCD. MCD was diagnosed through kidney biopsy. Exclusion criteria encompassed secondary nephrotic syndrome, malignancy, a history of severe adverse events during rituximab treatment, serologic evidence of active hepatitis B infection, known history of human immunodeficiency virus infection, and active cytomegalovirus infection. The patients subsequently received either obinutuzumab or glucocorticoids (GC). The primary endpoint was treatment response, which was defined as complete remission (CR) of nephrotic syndrome. The secondary measures included infection and relapse. Results Among the 37 participants, 15 received obinutuzumab and 22 received GC. The median age was 49.0 years (IQR, 26.5–66.5), and the median duration of MCD was 20.0 days (IQR, 13.0–60.0). The median level of proteinuria was 8.7 g/day (IQR, 5.8–12.0), the median serum albumin level was 19.6 g/l (IQR, 17.7–23.4), and the median serum creatinine level was 73.0 µmol/L (IQR, 64.0–117.5). The mean eGFR was 84.3 ± 34.1 ml/min/1.73 m2. There were no significant differences in proteinuria levels, serum creatinine levels, eGFR, diabetes mellitus and hypertension at baseline between two groups. Participants in the obinutuzumab group were older than participants of GC group, 67.0 (34.0, 72.0) vs. 43.0 (23.0, 56.5), P = 0.044. Duration of MCD in obinutuzumab group was longer than that of GC group. Participants in the obinutuzumab group had higher level of serum albumin and HbA1c. In the obinutuzumab group, 11 the of 15 participants (73.3%) achieved CR during a median follow-up of 28 days (IQR 20.0–40.0). In the GC group, 20 the of 22 participants (90.9%) achieved CR, during a follow-up of 21 days (IQR, 14.0–42.0). There were 5 participants (22.7%) relapsed in GC group. Meanwhile, none patient was observed relapse in the obinutuzumab group. The relapse rate of GC group was significantly higher than the obinutuzumab group. The infection rate of the GC group was higher than that of the obinutuzumab group (40.9% vs. 13.3%, P = 0.072), but the difference did not reach statistical significance. Kaplan-Meier curves demonstrated that there was no significant difference in the CR rate between the obinutuzumab group and the GC group (log rank χ2 = 1.639, P = 0.200; Fig. 2). Univariate regression analysis showed that duration of MCD and obinutuzumab treatment were significantly associated with CR rate (P < 0.05). Hypertension and proteinuria levels were also associated with CR rate (P < 0.1), which were put in the multivariate Cox regression analysis. Multivariate Cox regression showed that the treatment of obinutuzumab or GC was not independently associated with CR rate after adjusting for covariates. Conclusion In this study, we compared the effectiveness of obinutuzumab versus GC as an initial treatment for adult MCD patients. The results of this study showed that the induction regimen of obinutuzumab alone can achieve clinical remission in MCD patients, especially those with previous steroids resistant/dependent, longer duration of MCD, elderly, high levels of BMI and HbA1c, avoid the side effects of steroids, and reduce the relapse in MCD patients. This retrospective study is the first study demonstrated that obinutuzumab alone as the initial therapy can effectively induce and maintain remission and can be applied as an alternative to GC therapy in adult MCD patients.