Obinutuzumab 1g/40ml solution for infusion vials

OBJECTIVE: Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN in combination with standard therapies. METHODS: Patients with LN receiving mycophenolate and corticosteroids were randomised to obinutuzumab 1000 mg or placebo on day 1 and weeks 2, 24 and 26, and followed through week 104. The primary endpoint was complete renal response (CRR) at week 52. Exploratory analyses through week 104 were conducted. The prespecified alpha level was 0.2. RESULTS: A total of 125 patients were randomised and received blinded infusions. Achievement of CRR was greater with obinutuzumab at week 52 (primary endpoint, 22 (35%) vs 14 (23%) with placebo; percentage difference, 12% (95% CI -3.4% to 28%), p=0.115) and at week 104 (26 (41%) vs 14 (23%); percentage difference, 19% (95% CI 2.7% to 35%), p=0.026). Improvements in other renal response measures, serologies, estimated glomerular filtration rate and proteinuria were greater with obinutuzumab. Obinutuzumab was not associated with increases in serious adverse events, serious infections or deaths. Non-serious infusion-related reactions occurred more frequently with obinutuzumab. CONCLUSIONS: Improved renal responses through week 104 were observed in patients with LN who received obinutuzumab plus standard therapies compared with standard therapies alone. Obinutuzumab was well tolerated and no new safety signals were identified. TRIAL REGISTRATION NUMBER: NCT02550652.

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ABSTRACT: In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events. Patient reported outcomes of time until definitive deterioration (TUDD) in quality of life (QoL) were analyzed. At a median observation time of 76.4 months, PFS remained superior for Ven-Obi compared with Clb-Obi (median, 76.2 vs 36.4 months; hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.31-0.52; P < .0001). Likewise, TTNT was longer after Ven-Obi (6-year TTNT, 65.2% vs 37.1%; HR, 0.44; 95% CI, 0.33-0.58; P < .0001). In the Ven-Obi arm, presence of del(17p), unmutated immunoglobulin heavy-chain variable region, and lymph node size of ≥5 cm were independent prognostic factors for shorter PFS. The 6-year OS rate was 78.7% in the Ven-Obi and 69.2% in the Clb-Obi arm (HR, 0.69; 95% CI, 0.48-1.01; P = .052). A significantly longer TUDD in global health status/QoL was observed in the Ven-Obi than in the Clb-Obi arm (median, 82.1 vs 65.1 months; HR, 0.70; 95% CI, 0.51-0.97). Follow-up-adjusted second primary malignancies incidence rates were 2.3 and 1.4 per 1000 patient-months in the Ven-Obi and Clb-Obi arm, respectively. The sustained long-term survival and QoL benefits support the use of 1-year fixed-duration Ven-Obi in CLL. This trial was registered at www.ClinicalTrials.gov as #NCT02242942.

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Background: Obinutuzumab, a new-generation anti-CD20 monoclonal antibody, was originally developed to overcome resistance to rituximab in B-cell malignancies. There is limited research regarding the use of obinutuzumab in patients with rituximab-refractory membranous nephropathy (MN) and minimal change disease (MCD). Methods: A retrospective analysis was performed at Changzheng Hospital from September 2022 to September 2024, and screened patients with rituximab-refractory MN or MCD. Participants were treated because they were refractory to rituximab and consented to receive infusions of obinutuzumab. Primary outcomes were defined as complete remission (CR, proteinuria <0.3 g/d) or partial remission (PR, proteinuria <3.5 g/d with a ≥50% reduction). Secondary outcome was immunological remission in patients with phospholipase A2 receptor (PLA2R)-related MN. Results: Seven patients with MN and five with MCD were included in the cohort. Among patients with MN, six of seven (86%) achieved at least PR, of whom two patients reached CR with a median time to first remission (either PR or CR) of 8.0 months. Among patients with positive serum anti-PLA2R antibodies at baseline, all achieved an immunological response. No patients experienced a relapse during the follow-up period. Among patients with MCD, all patients achieved a CR with the median time of 1.0 months. Patients who were steroid-dependent or immunosuppressant-dependent were able to taper their medications in the short term without experiencing relapse. No treatment-related severe adverse events were reported. Conclusions: Our study demonstrated that obinutuzumab represents a promising alternative therapeutic option for the management of rituximab-refractory MN and MCD.

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Membranous nephropathy (MN) is a kidney disease characterized by thickening of the glomerular basement membrane due to immune complex deposition, often leading to nephrotic syndrome and potentially progressing to end-stage renal disease. Traditional treatments, including corticosteroids and immunosuppressive agents, have significant side-effects and variable efficacy. Recently, obinutuzumab, a fully humanized monoclonal antibody targeting CD20, has emerged as a promising therapeutic option for MN. Herein, we review the pathophysiology of MN, the mechanism of action of obinutuzumab, clinical data supporting its use and highlight its potential as a game changer in MN treatment.

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Obinutuzumab is a humanized type II anti-CD20 monoclonal antibody that is widely used in B-cell lymphomas including follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Multiple clinical studies have shown that compared with rituximab combined with chemotherapy, obinutuzumab combined with chemotherapy can significantly improve the progression-free survival (PFS) of patients, effectively reduce the risk of disease progression, and improve patient prognosis. The main adverse effects of obinutuzumab include infusion reactions, myelosuppression, infection, cardiotoxicity, tumor lysis syndrome (TLS), etc., and in rare cases it may induce thrombocytopenia. However, so far there are few reports on "obinutuzumab-induced acute thrombocytopenia" (OIAT), especially severe cases. Here, we report a case of acute severe OIAT and review the literature to explore the management of this rare but life-threatening complication. The case is a 28-year-old young man who was diagnosed with stage IV follicular lymphoma and achieved remission after 8 cycles of R-CHOP chemotherapy. Later, he developed severe acute thrombocytopenia during maintenance treatment with obinutuzumab monotherapy, the patient's platelet count dropped from 191×10^9/L to 2×10^9/L on the 3rd day after the initial application, and severe thrombocytopenia occurred after multiple subsequent applications of obinutuzumab. OIAT is a rare but life-threatening complication. We should be aware of this adverse event and raise awareness about it.

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