Abstract: TH-PO1206
Single-Center, Phase 2, Open-Label Trial Evaluating the Efficacy and Safety of Obinutuzumab in Treatment of Immunosuppression-Resistant Primary FSGS, or Contraindication to High-Dose Corticosteroids
Session Information
- Late-Breaking Science Posters
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Zand, Ladan, Mayo Clinic Department of Internal Medicine, Rochester, Minnesota, United States
- Greene, Eddie L., Mayo Clinic Department of Internal Medicine, Rochester, Minnesota, United States
- Cheungpasitporn, Wisit, Mayo Clinic Department of Internal Medicine, Rochester, Minnesota, United States
- Vargas-Brochero, Maria Jose, Mayo Clinic Department of Internal Medicine, Rochester, Minnesota, United States
- Machado, Miriam, Mayo Clinic Department of Internal Medicine, Rochester, Minnesota, United States
- Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Ronco, Pierre M., Hopital Tenon, Paris, Île-de-France, France
- Fervenza, Fernando C., Mayo Clinic Department of Internal Medicine, Rochester, Minnesota, United States
Background
We investigated the efficacy and safety of obinutuzumab, a type II anti-CD20 antibody, in patients with primary FSGS who were resistant/dependent on immunosuppressive therapy.
Methods
Patients were treated with 2 doses of obinutuzumab (1 gram), 2 weeks apart at baseline and 6 months. Primary outcome was change in proteinuria from baseline to 6 and 12 months. Secondary endpoints were complete (proteinuria <0.3g/d) or partial (50% reduction in proteinuria & proteinuria < 3.5 g/d) remission, & rates of serious adverse events.
Results
Twenty patients were enrolled. Average age 45.3±17.5 years, 55% male. Systolic BP: 132±17.5 mmHg, diastolic BP: 77.1±9.5 mmHg. Patients had failed 2-3 prior therapies. There was significant improvement in proteinuria: baseline [10.7 (7.5 – 13.7)] g/d to 12 months [3.8 (1.5 – 8.6)] g/d (p=0.001), significant improvement in serum albumin, cholesterol, & eGFR (Table 1). By 12 months, 8 patients (40%) reached CR/PR, none relapsed. 3 serious adverse events (SAE): 2 in one patient hospitalized for suicidal ideation and pseudo-seizures, 1 SAE was development of follicular lymphoma. SAEs were unrelated to obinutuzumab. Most common AE was infusion-related reaction occuring in 7 patients (none resulted in therapy discontinuation). There were 7 infections, none required hospitalization.
Conclusion
Obinutuzumab significantly reduced proteinuria in patients with primary FSGS who had failed 2-3 prior therapies. Reduction in proteinuria was associated with an improvement in eGFR and serum albumin with an acceptable side effect profile.
Patients laboratory and urine study data
| Baseline N=20 | 6 months (N=20) | 12 months N=20 | P-value* | |
| Serum creatinine (mg/dL) | 1.67 ± 0.83 | 1.65 ± 0.81 | 1.44 ± 0.81 | 0.15 |
| eGFR (ml/min/1.73m2) | 48 (28, 89) | 48 (34, 93) | 62 (37, 95) | 0.04 |
| Serum albumin (g/dL) | 2.5 ± 0.6 | 3.1 ± 0.8 | 3.5 ± 0.8 | <0.001 |
| Total cholesterol (mg/dL) | 285 ± 120 | 277 ± 132 | 213 ± 49 | 0.002 |
| LDL cholesterol (mg/dL) | 194 ± 122 | 175 ± 148 | 122 ± 40 | 0.008 |
| Proteinuria (g/d) | 10.7 (7.5, 13.7) | 7.3 (4.0, 10.3) | 3.8 (1.5, 8.6) | 0.001 |
| B-cell counts (cells/μl) | 160 (75, 251) | 0 (0, 1) | 0 (0, 0) | <0.001 |
*p-value is the comparison between baseline and 12 months (paired t-test or Wilcoxon test). Results are reported as averages ± SD or median and interquartile range.
Funding
- Commercial Support – Genentech