Rituximab Therapy Research Articles

#1315 Management and long-term outcome of recurrent idiopathic FSGS in pediatric renal transplant recipients

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is a leading cause of pediatric end-stage renal disease (ESRD). While approximately 30% of pediatric FSGS is attributed to monogenic disorders, most cases are idiopathic, carrying a high risk of post-transplantation recurrence and graft loss. Commonly used protocols for recurrent FSGS (rFSGS) include plasmapheresis or immunoadsorption, and/or immunomodulatory therapy. We retrospectively evaluated the efficacy and safety of early plasmapheresis followed by rituximab therapy for induction of remission in rFSGS. Method Between 2014-2023, 8/65 pediatric renal transplant recipients at our center were diagnosed with idiopathic FSGS. Five patients underwent preventive plasmapheresis initiated between day 7 pre-transplantation to day 1 post-transplantation, depending on donor source (living/deceased). rFSGS, was diagnosed based on nephrotic range proteinuria of no other cause, and managed with daily plasmapheresis, followed by frequency tapering. Failure to achieve complete remission while on prolonged plasmapheresis was managed with Rituximab therapy. Results 6/8 patients (75%) experienced rFSGS. All achieved partial or complete remission with plasmapheresis therapy. Nevertheless, 5/6 patients exhibited plasmapheresis-dependence, thereby necessitating rituximab therapy. Of these, 3/5 patients achieved sustained remission enabling plasmapheresis cessation, while in 2/5 showed markedly improved proteinuria, enabling reduction of plasmapheresis frequency to once weekly. Adverse effects included rituximab-induced serum sickness in one patient, requiring therapy discontinuation. While one patient suffered from graft loss due to humoral rejection, no graft was lost to rFSGS, and all other grafts remained functional over an average follow-up period of 50 months. Conclusion We suggest that early introduction of plasmapheresis and rituximab therapy effectively induces remission in most post-transplantation rFSGS, is well tolerated, and prevents graft loss. Additional, large scale studies are needed to establish our observation.

#2684 Free light chains levels in ANCA associated vasculitis: a new potential inflammatory biomarker

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic disease characterized by an immune-mediated process where inflammation plays a central role. The widely available serum biomarkers of inflammation are not always able to detect ongoing disease activity in ANCA-associated vasculitis (AAV) patients. Free light chains (FLCs) expression levels have been proposed as new promising biomarker in some immune-mediated and inflammatory diseases. The aim of this study is to evaluate the expression levels of FLCs in patients affected by AAV and investigate the potential effect of rituximab treatment on FLCs levels. Method We conducted a retrospective multicenter study enrolling AAV patients in complete remission of AAV (defined as BVAS/GPA = 0); those with clinical suspicion of underlying hematologic malignancy were excluded. We analyzed κ and λ FLCs serum concentrations and evaluated their correlation with biomarkers of immune system activation, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum immunoglobulin (Ig) levels, serum C3 and C4 complement and albumin levels (which has a negative correlation with acute inflammatory phase). We assessed impact of rituximab (RTX) therapy within the last 6 months on the same laboratory parameters. Results A total of 137 patients with AAV were recruited, who were gender balanced, had an average age of 68 years and an estimated glomerular filtration rate of 68 (43-89) mL/min/1.73 m2. Fifty-one patients received rituximab treatment (RTX group), while 86 patients were on other immunosuppressive maintenance therapies (non-RTX group). In comparison to non-RTX group, patients treated with RTX experienced higher complement C3 levels, lower ESR levels and lower FLCs κ (p = 0.063) and λ (p = 0.013) levels. The differences between RTX and non-RTX groups in terms of FLCs were even more prominent after correction to total Ig concentration (p = 0.004 for κ /Ig and p = 0.003 for λ /Ig, respectively). Both, serum free κ and λ levels were found to correlate significantly with ESR (R = 0.55 and p < 0.001 for κ; R = 0.53 and p < 0.001 for λ) and albumin (R = ‒0.38 and p < 0.001 for κ; R = ‒0.33 and p < 0.001 for λ). Additionally, serum free κ levels showed an inverse association with C3 (R = ‒0.18 and p = 0.041). Conclusion In subjects with AAV, FLC levels were found to be associated with markers of inflammation and complement activation; hence FLCs levels may represent a promising biomarker for detection of subclinical inflammation in AAV patients on maintenance therapy. Rituximab therapy showed a potential to reduce the levels of markers of subclinical inflammation, including FLCs.

Case report: Isolated immunoglobulin G4-related sclerosing cholangitis misdiagnosed as hilar cholangiocarcinoma

BackgroundImmunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied with AIP is uncommon in clinical practice, and its manifestations are similar to those of hilar cholangiocarcinoma.Case presentationA 55-year-old male presented with persistent aggravation of icteric sclera and skin. He was initially diagnosed with hilar cholangiocarcinoma and underwent surgery. However, positive IgG4 plasma cells were found in the surgical specimens. Thus, a pathological diagnosis of IgG4-SC was established. After that, steroid therapy was given and initially effective. But he was steroid dependent, and then received rituximab therapy twice. Unfortunately, the response to rituximab therapy was poor.ConclusionIt is crucial to differentiate isolated IgG4-SC from hilar cholangiocarcinoma to avoid unnecessary surgery. Future studies should further explore effective treatment strategy in patients who do not respond to steroids therapy. It is also required to develop novel and accurate diagnostic approaches to avoid unnecessary surgical procedures.

#1577 Rituximab in patients with primary podocytopathies: case series

Abstract Background and Aims Rituximab (RTX) has been reported as an effective treatment alternative in primary forms of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with steroid dependence and frequent relapses. However, the optimal RTX regimen and the outcomes of further doses of RTX remain unclear. This study aimed to evaluate the use of induction and maintenance RTX therapy for adults with primary podocytopathies. Method We performed a retrospective case series on adult patients with steroid-dependent podocytopathies who received an induction RTX therapy. Maintenance therapy was performed at physician's discretion. Remission and relapse rates, concomitant corticosteroids and immunosuppressants use, B-cell depletion and adverse events were analyzed. Results Fourteen patients (mean age at start of RTX 29.1 ± 21.9 years) with MCD (n = 7) or FSGS (n = 7) were treated with 2 doses of 1000 mg 2 weeks apart (n = 13) or four doses of 375 mg/m2 (n = 1) of RTX. At last follow-up (mean 47.3 ± 101.7 months) ten patients were in complete remission and two remained in partial remission. A reduction in the number of relapses, number of patients under corticosteroids and immunosuppressants, and dose of prednisolone was observed when compared to baseline [14 (100%) vs 5 (35.7%); 8/14 (57.1%) vs 4/12 (33.3%); 13/14 (92.9%) vs 7/12 (58.3%); 20 mg/day vs 5.25 mg/day, respectively]. Maintenance RTX therapy was used in six patients, with sustained complete remission. Infusion reactions were observed in four patients (one required treatment withdrawal). Conclusion Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.

#3076 A UK parallel cohort study on renal ANCA associated vasculitis outcomes for avacopan exposed and matched unexposed cohorts

Abstract Background and Aims Avacopan was approved in the UK for severe ANCA associated vasculitis (AAV) in December 2022. The ADVOCATE trial found the differential effect of avacopan on kidney function was greatest in patients with the lowest estimated glomerular filtration rate (eGFR), at highest risk of progression to end stage kidney disease (ESKD). Patients with an eGFR <15 ml/min/1.73 m2, pulmonary haemorrhage requiring invasive ventilation, under 12 months prognosis, use of plasma exchange and dual therapy with cyclophosphamide (CYC) and rituximab (RTX) were excluded from ADVOCATE; all common scenarios in real life practice. We aim to provide further information on these subgroups and evaluate 6 month renal outcome data in the UK. Method Parallel cohort study on renal AAV outcomes for avacopan exposed and matched unexposed cohorts, with severe, active GPA or MPA. 120 patients on avacopan from 7 UK centres have been recruited to date. Controls matched by renal function and age will be presented. Comparisons of ESKD, delta eGFR, eGFR recovery, reduction in proteinuria/haematuria, remission, relapse and mortality will be presented, with subgroup analyses for eGFR<15 ml/min/1.73 m2. Steroid exposure will be presented. Results Baseline characteristics of the avacopan cohort are below. Most received oral prednisolone at avacopan initiation (89%, n = 107) and 54% received intravenous methylprednisolone (n = 65). The majority received RTX alone (44%, n = 53) or RTX and CYC combination therapy (43%, n = 52). Fewer received CYC alone (9%, n = 11) and 3% were initiated on alternative immunosuppression (n = 4). 26% (n = 31) underwent plasma exchange and 13% required haemodialysis (n=16). 3% of patients have died. Excluding dialysis dependent patients at presentation, median eGFR was 22ml/min/1.73 m2 (IQR 10-36). eGFR at the time of avacopan initiation was 21ml/min/1.73 m2 (IQR 11-34). Conclusion Avacopan is commonly being used to treat nephritis in patients with a low eGFR, including haemodialysis dependent and elderly patients. Avacopan is frequently used with RTX and CYC combination therapy. 6 month outcome data will provide new data on important patient subgroups excluded from the ADVOCATE trial.

#2691 Treatment naive membranous nephropathy patients treated with rituximab in COVID19 era

Abstract Background and Aims Standard of care of high-risk idiopathic membranous nephropathy patients is immunosuppressive treatment with cyclophosphamide and corticosteroids or rituximab. Our aim was to assess outcome and safety of rituximab therapy in COVID19 era in comparison to modified Ponticelli protocol. Method In this retrospective study all adult patients with biopsy proven membranous nephropathy treated with rituximab as a first line therapy from 2020 till 2022 were enrolled and compared with MN patients treated with modified Ponticelli protocol from 2013 till 2020. Renal outcome was defined as composite of partial and complete remission defined according KDIGO guidelines. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels. Results During the COVID 19 era, between 2020 and 2022, 8 MN patients were treated with rituximab as a first line therapy. One was lost from follow up and one had allergic infusion reaction and therefore was excluded from further analysis. Ten patients were treated with modified Ponticelli protocol. There was no difference in age (60 vs. 59 years; p = 0.669), gender (M 57.1 vs. 60%), BMI (26.3 vs. 29.1cm/kg; p = 0.906), systolic (140. vs. 150 mmHg; p = 0.161) or diastolic (90 vs. 91.5 mmHg; p = 0.230) blood pressure between rituximab and cyclophosphamide treated group. Also, there was no difference in proteinuria between rituximab and cyclophosphamide treated group (16.2 (5.7–31.3) vs. 8.7 (6.5–12.5) g/dU; p = 0.201) Patients treated with cyclophosphamide had lower eGFR compared with patients treated with rituximab (51 (34-79) vs. 93 (72-98) ml/min/1,73 m²; p = 0.005). At 6 months follow up only 2 (28.6%) in rituximab group and 6 (60%) in cyclophosphamide group achieved outcome defined as composite of complete and partial remission. At one year follow up, there was no difference in outcome between groups and all patients from rituximab group compared to 8 patients (88.9%) from cyclophosphamide group accomplished composite favorable renal outcome (p = 398). At the end of follow up, one year after cyclophosphamide therapy eGFR was better (57 (43-96) vs. 51 (34-79) ml/min/1,73 m²). Rituximab was safe in our cohort. Three (50%) of patients acquired SARS CoV2 infection and there was no adverse outcome regarding COVID 19 disease. Conclusion Cyclophosphamide is faster than rituximab in accomplishing remission of nephrotic syndrome and improves deteriorated kidney function. Nevertheless, at 1 year follow up rituximab efficiency is proven to be excellent. Cyclophosphamide should be reserved for MN patients with nephrotic syndrome with reduced glomerular filtration rate.

A case diagnosed with IgA nephropathy during a complete remission of minimal change nephrotic syndrome treated with rituximab.

We herein report a case of IgA nephropathy in a 20-year-old male who maintained a complete remission of minimal change nephrotic syndrome (MCNS) through the administration of rituximab (RTX). He was diagnosed with nephrotic syndrome at 4years of age. After he relapsed frequently, he was diagnosed with MCNS at 8years of age based on the findings of a kidney biopsy. At 13years of age, RTX therapy was initiated to maintain a complete remission after steroid treatment. MCNS recurred twice, including the time in which the interval between the RTX administrations was long. Whenever he relapsed, remission induction was achieved using steroids, and remission maintenance was achieved using RTX. Five months after the 7th RTX administration, the serum IgA level started to increase. After the 9th RTX administration, he demonstrated microhematuria despite the urinary protein level indicating complete remission. At the 10th administration, the urinary protein and the red-blood cell casts were also observed. A renal biopsy was performed 84months after the initial administration of RTX, and the patient was diagnosed with complications of IgA nephropathy. RTX is not considered to be a useful treatment for IgA nephropathy. The reasons for this are due to the fact that IgA1 does not decrease even following the administration of RTX, because B cells residing in the mucosa may not be deleted by RTX, and IgA production may also continue due to the presence of CD20- long-lived plasma cells. Even when administering RTX, if there are findings of glomerulonephritis on urine testing, the possibility of IgA nephropathy must be considered.

Rituximab for rheumatoid arthritis-related interstitial lung disease: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed at summarizing the evidence of efficacy and safety of rituximab in rheumatoid arthritis-related interstitial lung disease (RA-ILD). PubMed and Embase databases were searched until June 22, 2022, to identify studies on RA-ILD treated with rituximab, confined to predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies to assess the overall stabilization or improvement in ILD, changes in percent-predicted (%-predicted) forced vital capacity (FVC), and %-predicted diffusion capacity of lungs for carbon monoxide (DLCO) following rituximab therapy. A total of 15 studies (4 prospective and 11 retrospective studies) were included, with a total of 314 patients. There were 105 (60.7%) females out of 173 subjects for whom sex details were available from seven studies. The overall pooled proportion of patients with stabilization or improvement in ILD was 0.88 [95% confidence interval (CI): 0.76-0.96, p=0.02]. Rituximab improved FVC from baseline by 7.50% (95% CI: 1.35-13.65; p=0.02, fixed effect). Similarly, rituximab improved DLCO by 6.39% (95% CI: 1.366-14.43; p=0.12, random-effect). Two retrospective studies reported reduced mortality with rituximab therapy compared to tumor necrosis factor-alpha inhibitors. Treatment with rituximab in RA-ILD was associated with a significant improvement in %-predicted FVC, as well as stabilization or improvement in ILD after one year of treatment.

Rituximab treatment in resistant lupusnephritis: A single-center prospective study.

Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE) and failure to respond to traditional immunosuppression increases morbidity and mortality. Rituximab has been considered a novel therapeutic option for the management of SLE. We conducted a single-center, prospective, observational study from July 2018 to June 2019 to evaluate the effectiveness of rituximab in patients with resistant LN. Resistant LN was defined as the failure to respond to conventional immunosuppressive therapy including both cyclophosphamide and mycophenolate mofetil. All adult patients (>18 years) with biopsy-proven class III/IV LN were included in the study. Four doses of intravenous rituximab (375 mg/m2) on 0, 1, 2, 3 weeks were administered. Patients were followed for 6months, and the rates of complete renal response (CRR), partial renal response (PRR), or no renal response (NRR) were measured. The change in baseline 24-hour urine protein, mean serum creatinine levels, and mean serum CD-19 levels at 24 weeks were also measured. Six months after rituximab therapy, total sustained renal response (CRR+PRR) was observed in 52% cases of resistant LN (CRR was achieved in 24% of patients and PRR in 28%, respectively). Rituximab was associated with a significant decline in the 24-hour urine protein, even in non-responders. However, the improvement in eGFR and serum creatinine was not statistically significant. The mean absolute CD-19 count was significantly low in responders compared to the non-responder group. Rituximab is a safe and effective therapeutic strategy for patients with resistant LN.

E018 Prophylactic co-trimoxazole prescribing practice in patients who received rituximab therapy: comparison across indications and specialties

Abstract Background/Aims Rituximab is a chimeric anti-CD20 monoclonal antibody targeting B-cells used as part of treatment algorithms for malignancy and autoimmune diseases. As is the case of other immunosuppressive agents, rituximab increases the risk of infections. Primary prophylaxis with co-trimoxazole may be considered in high-risk cohort of patients to prevent opportunistic infection, particuarly Pneumocystis jerovecii pneumonia (PJP). To investigate the prescribing practice for prophylactic co-trimoxazole in patients who received rituximab infusion in a large tertiary referral centre. To compare practices between rheumatology and nephrology department. To compare the incidence of hospitalisation for infection (particularly PJP) between those prescribed prophylactic co-trimoxazole and those who did not. Methods This was a single centre retrospective observational study over a 3 year period assessing prophylactic co-trimoxazole prescribing practice in 185 patients attending rheumatology or renal services in Cork University Hospital (CUH) and receiving rituximab. Co-trimoxazole prophylactic treatment was defined as prophylaxis dose of co-trimoxazole (either 480mg daily or 960mg three times per week) received during rituximab treatment and at least 6 months post completion of treatment. Results 185 patients’ medical charts were reviewed. Only 28 patients received prophylaxis with co-trimoxazole. The majority of patients (n = 24, 85%) who received prophylaxis with co-trimoxazole had an underlying diagnosis of small vessel vasculitis (SVV). Co-trimoxazole was more commonly prescribed by nephrologists (n = 17, 71% primarily for SVV) as compared to rheumatologist (n = 7, 29% primarily for SVV). 156 patients were not prescribed prophylactic co-trimoxazole. The primary indication for rituximab in these patients was inflammatory arthropathy (IA) (n = 72,46%), SVV (n = 26, 16%), systemic lupus erythematosus (n = 19, 12%), with the remainder accounted for by scleroderma, undifferentiated connective tissue disease, membranous nephropathy (MN), myositis, focal segmental glomerulosclerosis and amyloid renal disease. No patient was admitted over the course of the study period with PJP. 59 patients required hospital admissions due to other infections, most commonly patients with SVV. The most common infections were respiratory tract and urinary tract infections. Overall infections requiring hospitalization were more common in the group receiving prophylaxis, perhaps highlighting the vulnerable nature and greater prednisolone prescribing in the SVV cohort. No difference was seen between groups in the prevalence of UTIs. Conclusion In this cohort co-trimoxazole prophylaxis was more commonly prescribed for patient with small vessel vasculitis and differences in prescribing patterns were seen between nephrologists and rheumatologists. With greater awareness of the heightened risk of PJP in patents receiving rituximab consideration should be given to use of antibiotic prophylaxis for other indications. Disclosure S. Tio: None. J. Morrow: None. S. Cowley: None. M. Clarkson: None. G. Murphy: None.

Advancements in immunotherapy for glomerulonephritis: Promising treatments on the horizon.

Madam, Over the years, glomerulonephritis management has been predominantly reliant on corticosteroids and immunosuppressive agents. However, emerging research on targeted immunotherapies, such as biologics and monoclonal antibodies, has shown remarkable potential in halting the disease progression and promoting remission in certain glomerular disorders [1]. Glomerulonephritis, characterised by the inflammation of glomeruli, poses a significant burden on the health system of low-income countries. A study revealed that glomerulonephritis is the most common cause of end-stage renal disease in developing countries, and it affects at least 21% of the adult population in Pakistan [2]. The emergence of novel immunotherapeutic approaches may revolutionise treatment outcomes, offering new hopes for patients suffering from this complex and challenging kidney disorder in Pakistan. An extensive study assessed the role of Belimumab, a B-lymphocyte stimulator (BLyS) inhibitor, in patients with lupus nephritis. The monoclonal antibody, Belimumab showed promising outcomes in patients with lupus [3]. Another recent study revealed that rituximab, a monoclonal antibody to CD20 can be used for patients suffering from ANCA Glomerulonephritis or also in patients with steroid resistance [4]. These findings demonstrated a substantial reduction in proteinuria and in increased remission rates following rituximab therapy, highlighting its potential as a promising treatment option. According to a current study, dealing with glomerulonephritis in low-resource setting areas in Pakistan is very challenging as it's only limited to tertiary care hospitals [5]. As the landscape of glomerulonephritis management evolves, it is crucial to encourage further research and clinical trials to establish immunotherapies' long-term efficacy and safety. Collaborative efforts among nephrologists, researchers, and pharmaceutical companies can drive the development of personalized treatment strategies, optimising patient care and outcomes. In conclusion, immunotherapy for glomerulonephritis holds immense promise, with encouraging results emerging from research conducted in Pakistan and around the globe. The government should build some nephrology centres in areas devoid of tertiary settings so the patients can be treated on time. As we move toward an era of precision medicine, harnessing the potential of immunotherapeutic agents in glomerulonephritis treatment represents a beacon of hope for patients seeking effective and targeted therapies.

Rituximab or cyclosporine a for the treatment of membranous nephropathy: Economic evaluation of the MENTOR trial.

The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health care payers. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health care payer with a life-time time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced cost biosimilar rituximab. Rituximab for the treatment of membranous nephropathy was cost-effective (assuming a willingness-to-pay threshold of ${\$}$50000 per quality adjusted life year (QALY) gained; ${\$}$US 2021) compared with cyclosporine, with an ICER of ${\$}$8373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was ${\$}$28007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favourable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine. Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.

Higher Mortality in Patients With Diffuse Large B-cell Lymphoma Pre-Existing Arterial Hypertension—Real World Data of the Polish Lymphoma Research Group

Arterial hypertension is mentioned as a risk factor in cardio-oncology. This study aimed to assess the long-term prognostic value of arterial hypertension (AH) in diffuse large B-cell lymphoma (DLBCL). We analysed data collected by the Polish Lymphoma Research Group for the evaluation of the outcomes associated with the use of first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy in patients with DLBCL with coexisting AH. Patients with other cardiovascular comorbidities or premature chemotherapy discontinuation due to cardiovascular toxicity were excluded. Pre-existing AH was diagnosed in 65 of 232 patients with DLBCL (28%) included in the study, and was associated with significantly shorter overall survival values (p<0.00001). The rates of DLBCL recurrence, administration of second-, third-, or fourth-line chemotherapy, and lymphoma-related deaths were similar in patients with and those without AH. Cardiovascular deaths were significantly more frequently observed in patients with pre-existing AH (38.5% vs 3.6%, p<0.0001). In the univariate analysis, AH (p=0.000001), older age (p<0.000001), and diabetes (p=0.0065) were identified as significant predictors of all-cause mortality; however, cardiovascular mortality was associated with AH (p<0.000001), older age (p=0.000008), and dyslipidaemia (p=0.03). Multivariate analysis revealed AH as an age-independent significant predictor of all-cause (p=0.00045) and cardiovascular mortality (p<0.000001). In the long-term follow-up of patients with DLBCL, the role of AH, as an important age-independent predictor of premature cardiovascular mortality, was so strong that it may have value for use in close surveillance in cardio-oncology clinics.

Outcomes of Autologous stem cell transplantation in patients with primary refractory Diffuse Large B-cell lymphoma who demonstrate chemosensitivity to salvage chemotherapy.

Rituximab with anthracycline-based combination frontline chemoimmunotherapy can cure 50-60% of patients with diffuse large B-cell lymphoma (DLBCL). However, studies on the outcomes of patients with DLBCL who experience partial response (PR), stable or progressive disease in response to frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) therapy are limited, as are data on the outcomes of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in patients with primary refractory DLBCL who demonstrate chemosensitivity to salvage chemotherapy (SC). We assessed the latter among 184 patients, 144 of whom started SC, with 84 responding and 72 receiving HDC-ASCT. The 5-year survival rate was 58.9%; the median overall survival (OS) was not reached. The difference in response to SC (partial response versus complete response) was significant, with higher 2- and 5-year OS rates in patients with CR (78.1% and 74.9%, respectively) than in those with PR (55.3% and 47%, respectively). The median OS for the whole group was 15 months and particularly patients who had progressive disease after frontline R-CHOP had dismal outcomes. Our study suggests that in patients with primary refractory DLBCL without initial progressive disease after frontline R-CHOP, the depth of response to SC before HDC-ASCT is predictive of relapse.

Eruptive Nevus Following Rituximab Treatment: Unusual Dermoscopic Presentation: A Case Report

Background: Eruptive nevi can occur following various conditions, including the use of immunosuppressive and immunomodulatory drugs such as biologics. Dermoscopy typically reveals a pattern of brown globules arranged in a ring at the periphery. We report a case of eruptive nevus with an atypical dermoscopic pattern in a patient receiving Rituximab. Observation: A 37-year-old female patient, followed for acquired bullous epidermolysis, developed pigmented and extensive macules six months later. Dermoscopy of a lesion on the trunk, which was increasing in size, showed a homogeneous brown pattern with irregularly arranged brown globules and dots at the center and periphery. Biopsy revealed a junctional nevus. Conclusion: The atypical brown pattern on dermoscopy of eruptive nevi is described for the first time, particularly after rituximab therapy.

Autoimmune GFAP Astrocytopathy-Beyond the Known Horizon, India's First Multifaceted Institutional Experience.

Background: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an immune-mediated inflammatory disease of the central nervous system, the clinical phenotype of which includes meningoencephalitis, myelitis, optic neuritis, seizures, movement disorders, autonomic dysfunction among others, affecting people across all ages. Due to its recent discovery, there is a paucity of literature on this topic and an absolute lack of Indian case series. Purpose: This study aims to shed light on the variable presentations of anti-GFAP astrocytopathy and review the existing literature on the topic. Methods: This was a retrospective study that included all patients who tested positive in the cerebrospinal fluid(CSF) and/or serum for GFAP immunoglobulin G between February 2023 and August 2023, after obtaining ethical clearance. Relevant clinical, demographic data was collected from the electronic medical records. A descriptive analysis of data was done and the current available literature was reviewed. Results: Our case series included four patients (F:M::3:1) with a median age of 28 years at symptom onset. Two of the cases had a relapsing-remitting disease pattern, while the other two had monophasic illnesses. The clinical spectrum we encountered included ataxia, tremors, myoclonus, seizures, recurrent myelitis, brain stem syndromes, autonomic dysfunction and psychiatric manifestations. All four patients responded remarkably to steroids and two patients are on rituximab therapy. Conclusion: Autoimmune GFAP astrocytopathy encompasses an expanding clinical spectrum and should be considered in the context of myelitis, optic neuritis, ataxia, papillitis, seizures, autonomic dysfunction and movement disorders occurring in isolation or more commonly in varying combinations. Our case series, the first in India, shows a favourable clinical profile and the primary hurdle encountered in all four cases was to establish a diagnosis, further stressing the need for a predictive diagnostic algorithm.

Prevalence of primary headaches in multiple sclerosis patients

BackgroundMultiple sclerosis (MS) is the most common immune-mediated inflammatory disease of the central nervous system. It is characterized by symptoms such as visual disturbances, paresis with spasticity, paresthesia, numbness, and fatigue. However, several studies have shown a high prevalence of headaches in individuals with MS. Migraine and tension-type headaches are the most frequent types of headaches experienced by those with MS. Additionally, the role of MS disease-modifying agents must be considered. These agents have different modes of action and side effect profiles, and their use may sometimes trigger headaches in patients with MS. ObjectivesThis study aimed to explore the prevalence and clinical characteristics of primary headaches in MS patients. The relationship between headache and clinical features of MS (Course of MS, duration, EDSS, brain imaging and DMD) are also investigated. Subjects and MethodsTwo hundred and eighty-one MS patients diagnosed according to according to the 2017 revisions to the McDonald Criteria were included in the study. Data was collected from the MS unit medical records and from the interview with the patients. Patients with reported headaches are asked to recall their headache characteristics and patterns using an interviewer administered Arabic language-structured validated questionnaire. ResultsThe median age of patients was 33 years old, with a range of 22–55. Tension-type headache (TTH) was more common in males, patients with more severe disability (EDSS ≥ 3), and those with SPMS and PPMS phenotypes. Additionally, patients on rituximab or cyclophosphamide therapy were more likely to have TTH. On the other hand, females, patients with milder disability (EDSS < 3), and those with RRMS phenotype were more likely to have migraine. This was also true for patients with MRI lesions involving the periaqueductal gray, and those receiving INF or fingolimod (P < 0.05). Periaqueductal gray matter lesions were found in the MRI of 48 patients (40 %) who experienced headaches on more than 10 days per month. Sensorimotor lesions in the brain were found in 55 patients (53.4 %) with severe headaches (p-value < 0.001). Interferons were associated with an increased risk of worsening preexisting headaches and the appearance of de novo headaches related to its intake (odds ratio: 2.84, 3.72; relative risk: 1.63, 2.04; p-value = 0.03, < 0.001, respectively). On the other hand, rituximab was associated with a decreased risk of worsening preexisting headaches and the appearance of de novo headaches related to its intake (odds ratio: 0.04, 0.09; relative risk: 0.11, 0.18; p-value = < 0.001, < 0.001, respectively). ConclusionPrimary headaches are a common occurrence in patients with MS. Migraines and tension-type headaches (TTH) are among the most prevalent types. It has been observed that interferon can exacerbate preexisting headaches and even cause new ones. Additionally, the location of MS plaques may play a role in the frequency and severity of headaches.

Hepatitis B relapse after entecavir or tenofovir alafenamide cessation under anti-viral prophylaxis for cancer chemotherapy

BackgroundNo study has comparing hepatitis B virus (HBV) relapse rates among patients with both cancer and hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) who completed anti-viral prophylaxis for chemotherapy and then stopped taking entecavir or tenofovir alafenamide (TAF).MethodsA total of 227 HBeAg-negative cancer patients without cirrhosis who previously took entecavir (n = 144) or TAF (n = 83) for antiviral prophylaxis were enrolled.ResultsThe cumulative incidence of virological and clinical relapse at 2 years was 37% and 10.4%, respectively, in the entecavir group, and 46.7% and 19.5%, respectively, in the TAF group. The multivariate analysis revealed that the use of hematologic malignancy, TAF use, and high-viremia group at baseline were independent risk factors for virological relapse, and use of rituximab, TAF use, higher FIB-4 index and high-viremia group at baseline were independent risk factors for clinical relapse. After propensity score-matching, the patients who discontinued TAF therapy still exhibited higher virological (P = 0.031) and clinical relapse rates (P = 0.012) than did those who discontinued entecavir therapy. The patients were allocated to high- (> 2000 IU/mL), moderate- (between 20 and 2000 IU/mL) and low- (< 20 IU/mL) viremia groups. In the high-viremia group, those who had taken TAF for antiviral prophylaxis had higher rates of virological and clinical relapse than did those who had taken entecavir; in the moderate- and low-viremia groups, no significant difference in virological and clinical relapse rates was detected between the entecavir and TAF groups. Three patients experienced hepatic decompensation upon clinical relapse. All three patients were lymphoma and underwent rituximab therapy. One patient developed acute on chronic liver failure and died even though timely retreatment.ConclusionsIn patients with both cancer and CHB who underwent antiviral prophylaxis, TAF use was associated with a higher chance of HBV relapse than entecavir use after nucleos(t)ide analogue cessation, particularly in the high-viremia group. Patients who are hematologic malignancy and undergo a rituximab-containing cytotoxic therapy should be monitored closely after withdrawal from prophylactic NA treatment.

Frequency of Complete Remission With R-CHOP Therapy in Patients With Diffuse Large B Cell Lymphoma.

Background Diffuse large B-cell lymphoma (DLBCL) exhibits notable heterogeneity in clinical presentations and treatment responses, posing challenges in predicting outcomes and tailoring therapeutic strategies for affected patients. Despite advancements in molecular subtyping and prognostic assessment, uncertainties persist regarding the optimal management of DLBCL, highlighting the need for localized investigations to better understand treatment responses and outcomes within specific patient populations. Objective To assess the frequency of complete remission (CR) in diffuse large B-cell lymphoma (DLBCL) patients undergoing first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy within a specific adult population. Material and methods This descriptive study was conducted within the Department of Oncology Hayatabad Medical Complex, Peshawar, Pakistan from August 8, 2022, to April 8, 2023. The study included newly diagnosed DLBCL patients aged 20-70 years, excluding those who had received prior treatment. There were 55 (57.9%) males and 40 (42.1%) females. Data on demographic characteristics, disease duration, and CR outcomes were collected using a predefined data collection form. Results The majority of patients (80, 84.2%) achieved CR following R-CHOP therapy. In terms of age distribution, 43 (45.3%) patients were aged ≤45 years, while the remaining belonged to the >45 years age group. The duration of the disease was ≤ 3 months in 60 (63.2%) cases, whereas it exceeded three months in 35 (36.8%) cases. With regards to BMI classification, nine (9.5%) patients had a BMI < 18.5 kg/m2, 49 (51.6%) fell within the range of 18.5-24.9 kg/m2, and the remaining 37 (38.9%) patients had a BMI between 25-30 kg/m2. Conclusion Diffuse large B-cell lymphoma (DLBCL) remains a heterogeneous disease entity with variable clinical outcomes. While R-CHOP therapy demonstrates promising efficacy in achieving CR, concerns regarding late adverse effects persist. Addressing these challenges requires continued research efforts to validate novel prognostic markers and develop alternative treatment approaches, ultimately improving patient outcomes and reducing the global burden of DLBCL.

Electrodiagnostic Biomarkers in Paraneoplastic Retinopathy.

Paraneoplastic retinopathy (PNR) is a rapid-onset photoreceptor and post-photoreceptor dysfunction triggered by a cross-reaction between antigens expressed by the underlying tumour and retinal proteins. The present study aims to determine the electrodiagnostic biomarkers that support the diagnosis of PNR and evaluate the effect of treatment. A retrospective observational case-controlled study including 25 patients with suspected PNR, of which 11 patients were diagnosed with PNR. The presence of PNR was confirmed based on clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, optical coherence tomography, fluorescein angiography, retinal vessel oximetry, colour test, full-field electroretinogram (ffERG), on-/off ERG, S-cone ERG, and multifocal ERG (mfERG). The relationships between the clinical symptomatology and the effect of therapy were evaluated. All PNR patients (Nr: 11) presented with subjective symptoms of newly reported central vision or visual field deterioration. Posterior segment findings showed a severe patchy-like retinal atrophy, attenuation of the retinal vessels, and a waxy optic disc. Optical coherence tomography revealed a discontinued ISe line, and multiple hyperreflective foci. Retinal vessel oxygen saturation was increased. Multifocal ERG revealed reduced central and paracentral responses and ffERG severely attenuated scotopic-, photopic-, on-/off- and S-cone responses. The colour vision test revealed a tritan-tetartan-weakness. Two of the PNR patients underwent rituximab therapy with no further progression and even recovery of electrodiagnostic responses.In 1 nPNR (non-paraneoplastic retinopathy) patient (total Nr: 14) pseudoxanthoma elasticum-related retinopathy was the reason for impaired vision. In 3 of 13 patients with bronchopulmonary cancer a MEK- and FGFR-inhibitor- drug toxicity was the reason for the visual deterioration. Careful investigation for signs of central and/or peripheral visual field deterioration must be performed in the presence of history of a co-existing malignancy. The possibility of PNR should be taken into account. The electrodiagnostic biomarkers, suggested in this study, may help to promptly recognise PNR and also to evaluate the effect of implemented therapy.