Abstract: TH-PO0768
Second-Generation Monoclonal Anti-CD20 Antibodies in Podocytopathies
Session Information
- Glomerular Histopathology: Evolving Insights
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Angeletti, Andrea, Istituto Giannina Gaslini, Genoa, Liguria, Italy
- Caridi, Gianluca, Istituto Giannina Gaslini, Genoa, Liguria, Italy
- Kajana, Xhuliana, Istituto Giannina Gaslini, Genoa, Liguria, Italy
- Cravedi, Paolo, Mount Sinai Health System, New York, New York, United States
- Bigatti, Carolina, Mount Sinai Health System, New York, New York, United States
Background
Despite improvements in immunosuppressive regimens, a significant proportion of patients affected by podocytopathies remain refractory. Recent evidence suggests the involvement of autoantibodies. Therefore, the development of novel B-cell–targeted therapies has generated renewed interest. Obinutuzumab is a humanized type II anti-CD20 monoclonal antibody that has shown efficacy in glomerular diseases.
Methods
We conducted a proof-of-concept clinical trial to test the efficacy of obinutuzumab infusion (375 mg/mq) in steroid-dependent (SD) and steroid-resistant (SR) podocytopathies.
A total of 19 patients with SD disease were treated, and time to relapse following obinutuzumab was compared to prior rituximab.
Additionally, we treated 6 SR-podocytopathies who previously failed to rituximab and conventional oral immunosuppressive therapies.
B-cell depletion following obinutuzumab was compared to the degree achieved after rituximab administration.
Results
In SD patients, obinutuzumab administration resulted in longer relapse-free time compared to rituximab (Fig.1A).
All SR-podocytopathies achieved complete (n=3) or partial (n=3) remission within 3 months after obinutuzumab, which was maintained at 12 months of follow-up despite withdrawal of immunosuppressive drugs (Fig.1B).
Although B cell depletion did not statistically differ at 6 months after infusion compared to prior rituximab infusion in the same patients, it persisted at 12 months after obinutuzumab infusion (Fig.1C-D). This contrasts in part with the faster B cell recovery that occurs between 9 and 12 months after rituximab infusion (PMID: 34544820).
Overall, obinutuzumab resulted safety and well tolerated.
Conclusion
Our data indicate the potential of obinutuzumab to provide superior efficacy than rituximab in the treatment of podocytopathies across a spectrum of severity. The excellent safety/efficacy profile and the relatively long follow-up support further prospective studies to confirm these findings and define the utility of obinutuzumab in the treatment algorithm for podocytopathies.