UNASSIGNED: Minimal change disease (MCD) is a common cause of adult nephrotic syndrome. Most adults with MCD achieve complete remission (CR) after initial steroid therapy. However, approximately 30% of adults who respond to steroids experience frequent relapses, becoming steroid-dependent and potentially developing refractory MCD. Treating refractory MCD in adults poses a significant challenge.
UNASSIGNED: A 37-year-old woman presented to the nephrology department with a 6-year history of MCD. The diagnosis of MCD was confirmed via renal biopsy. She initially achieved CR with steroid treatment but experienced relapse during steroid tapering. Subsequent CR was achieved with a regimen of steroids and tacrolimus although multiple relapses occurred. Rituximab led to another CR, but its maintenance lasted only 6 months. The response to subsequent rituximab treatments was unsatisfactory. Ultimately, obinutuzumab was selected, resulting in the induction and maintenance of CR for 12 months.
UNASSIGNED: This case demonstrates the successful treatment of frequently relapsed, steroid-dependent, and rituximab-resistant MCD with obinutuzumab. Obinutuzumab is a promising therapeutic option for rituximab-resistant MCD.

CONCLUSIONS: In utero exposure to anti-CD20 monoclonal antibodies can result in transient B-cell depletion, delayed B-cell maturation, decreased immunoglobulin production and inadequate vaccine responses in the infant. These children require immunological follow up and personalized vaccine schedules.

UNASSIGNED: Obinutuzumab is a type II anti-CD20 monoclonal antibody associated with a higher rate of toxicity when compared to rituximab. Gastrointestinal side-effects have been reported but data is still sparse.
UNASSIGNED: A 47-year-old female with medical history of stage IV follicular non-Hodgkin lymphoma under chemotherapy presented with chronic bloody diarrhea and iron deficiency anemia. Endoscopic and histologic features resembled inflammatory bowel disease (IBD), imposing a thorough differential diagnosis. The diagnosis of obinutuzumab-induced pancolitis was made and the drug was suspended with subsequent clinical improvement.
UNASSIGNED: This is the first case report of obinutuzumab-induced pancolitis. The challenging differential diagnosis of IBD required a multidisciplinary approach with subsequent outcome and management implications.
UNASSIGNED: Obinutuzumab é um anticorpo monoclonal anti-CD20 tipo II, com aparente maior taxa de toxicidade relativamente ao rituximab. Alguns efeitos adversos gastrointestinais têm sido reportados, no entanto, a evidência científica mantém-se escassa.
UNASSIGNED: Mulher de 47 anos, com antecedentes de linfoma não-Hodgkin folicular estádio IV sob quimioterapia, apresenta-se com diarreia crónica sanguinolenta e anemia ferropénica. Os achados endoscópicos e histológicos assemelham-se a uma doença inflamatória intestinal (DII), impondo um diagnóstico diferencial exaustivo. Foi diagnosticada com uma pancolite induzida por obinutuzumab, tendo este sido suspenso, com melhoria clínica subsequente.
UNASSIGNED: Este é o primeiro caso documentado de pancolite induzida por obinutuzumab. A apresentação com aspetos sugestivos de DII obrigou a uma abordagem holística e multidisciplinar com implicações na abordagem e seguimento da doente.

Antibody-mediated complement-dependent cytotoxicity (CDC) on malignant cells is regulated by several complement control proteins, including the inhibitory complement factor H (fH). fH consists of 20 short consensus repeat elements (SCRs) with specific functional domains. Previous research revealed that the fH-derived SCRs 19-20 (SCR1920) can displace full-length fH on the surface of chronic lymphocytic leukemia (CLL) cells, which sensitizes CLL cells for e.g. CD20-targeting therapeutic monoclonal antibody (mAb) induced CDC. Therefore, we constructed lentiviral vectors for the generation of cell lines that stably produce mAb-SCR-fusion variants starting from the clinically approved parental mAbs rituximab, obinutuzumab and ofatumumab, respectively. Flow-cytometry revealed that the modification of the mAbs by the SCRs does not impair the binding to CD20. Increased in vitro lysis potency compared to their parental mAbs was corroborated by showing specific and dose dependent target cell elimination by CDC when compared to their parental mAbs. Lysis of CLL cells was not affected by the depletion of NK cells, suggesting that antibody-dependent cellular cytotoxicity plays a minor role in this context. Overall, this study emphasizes the crucial role of CDC in the elimination of CLL cells by mAbs and introduces a novel approach for enhancing CDC by directly fusing fH SCR1920 with mAbs.

UNASSIGNED: 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.
UNASSIGNED: A case series study.
UNASSIGNED: 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.
UNASSIGNED: Obinutuzumab treatment.
UNASSIGNED: Primary outcomes included remission rate, time to first remission, and first relapse-free survival time during the follow-up period.
UNASSIGNED: Survival analysis was performed with Cox proportional hazards models, log-rank test, and Kaplan-Meier survival analysis.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: Obinutuzumab demonstrated promising efficacy and safety in inducing remission in MN, particularly in patients with an unsatisfactory response to rituximab.
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.

URBAN is a multicentric, ambispective study evaluating the effectiveness and safety of obinutuzumab-based immuno-chemotherapy and maintenance in patients with untreated advanced follicular lymphoma (FL). The study began before the COVID-19 emergency declaration in Italy. It is currently ongoing for follow-up, and the enrolment timeline encompassed different stages of the pandemic, various vaccination roll-out phases and prevalence of SARS-CoV-2 variants. Outcomes of interest of the present sub-analysis included SARS-CoV-2 infection rates and COVID-19-related hospitalizations/deaths. At data cut-off, 86 (28.8%) and 213 patients (71.2%) were treated before and during/after the COVID-19 outbreak respectively; 294 (98.3%) completed the induction, 31 (10.4%) completed maintenance and 170 (56.9%) were still on maintenance. Overall, 245 patients (81.9%) received at least one SARS-CoV-2 vaccine dose: 13.5%, 31.4% and 55.1% received one, two and three doses respectively. We observed a substantial decrease in COVID-19-related mortality rates in pre- versus post-vaccination phases, along with a reduction in COVID-19-related outcomes due to the shift from alpha/delta to omicron variant predominance. No differences emerged between patients given maintenance or not, although the schedule was modified in 65% of cases. To our knowledge, URBAN represents the largest dataset of COVID-19-related outcomes in FL patients extensively exposed to obinutuzumab. ClinicalTrials.gov identifier: NCT04034056.

The recurrence of primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation is associated with a high graft loss rate with standard treatments based on plasmapheresis with/without rituximab. We present 2 consecutive cases of nongenetic early severe recurrent FSGS refractory to rituximab and anti-interleukin 1 treatment and with a partial response to plasmapheresis. Case 1 was a 22-year-old man who was rescue-treated for recurrence 36 weeks after transplantation with obinutuzumab (1000 mg/1.73 m2, 1 dose) and daratumumab (18 mg/kg each dose, 8 doses), resulting in plasmapheresis discontinuation and a drop of proteinuria from 29 to 2.3 g/d. Proteinuria increased with circulating CD38+ plasma cells and responded to an additional daratumumab dose. Currently, the proteinuria is 1.8 g/d, 14.5 months after discontinuing plasmapheresis and starting obinutuzumab and daratumumab therapy. Case 2 was a 15-year-old girl who was plasmapheresis dependent with 2 g/d proteinuria 82 weeks after transplantation, with a Tesio catheter in the right jugular vein as the only possible vascular access. After treatment with obinutuzumab and daratumumab (1 dose each), she achieved stable complete remission (0.3 g/d proteinuria) with persistent plasmapheresis discontinuation. These cases suggest the potential of combining obinutuzumab with daratumumab for the treatment of recurrent FSGS.

BACKGROUND: As an initial treatment for primary membranous nephropathy (PMN), there remains a significant proportion of patients for whom rituximab is not fully effective. Here, we aimed to assess the effectiveness and safety of obinutuzumab as initial treatment in patients with PMN.
METHODS: In this observational case series, patients diagnosed with PMN and treated with obinutuzumab as initial treatment were included. Treatment response was assessed by 24-h urine total protein (24 h UTP) and serum albumin, and immunologic remission was assessed by phospholipase A2 receptor (PLA2R) antibodies.
RESULTS: Twelve patients with PMN receiving obinutuzumab as initial treatment were included. Over 6 months, a statistically significant reduction in 24 h UTP levels (p = 0.003) and an increase in serum albumin levels were observed (p < 0.001). By the 6-month follow-up, two patients (16.7%) achieved complete remission, eight (66.6%) reached partial remission, and two (16.7%) showed no remission. Immunological remission was observed in 44.4% of evaluable patients (n = 9) after 3 months, increasing to 100% (6/6) at 6 months. Except for cases 1, 2, and 3, the total B cell counts in the remaining patients fell to less than 5 cells/μL before the administration of the second dose of obinutuzumab, including seven patients with counts as low as 0 cells/μL. Mild to moderate treatment-related adverse events (TRAEs) were reported in 58.3% (7/12) of the patients. No serious TRAEs were reported.
CONCLUSIONS: Obinutuzumab demonstrates promising potential as an initial treatment for PMN, with good effectiveness and a manageable safety profile. Further large-scale prospective studies are needed to confirm these findings.

A 69-year-old man was diagnosed with follicular lymphoma (Grade 3A). Obinutuzumab combined with bendamustine (OB) therapy was initiated as salvage chemotherapy. Nausea, abdominal pain, and hyponatremia appeared after six courses of OB therapy; cytomegalovirus (CMV) enteritis with primary adrenal insufficiency (PAI) was a complication. Ganciclovir and hydrocortisone were administered, and the clinical findings improved. PAI caused by CMV infection has mainly been reported in patients with acquired immunodeficiency syndrome. In the present case, the PAI triggered by CMV infection led to immunodeficiency after chemotherapy.

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