Cycles Of Rituximab Research Articles

Rituximab on lung, skin, and joint involvement in patients with systemic sclerosis: A case series study and review of the literature.

To evaluate the effectiveness of rituximab (RTX) in systemic sclerosis (SSc) patients. Data were collected from patient charts before and after RTX administration for 1year of follow-up time. An updated review of the literature was also done. Of 8 patients enrolled (mean age: 62.4years; mean disease duration: 16.7years), 2 patients with pulmonary arterial hypertension (PAH) died after the first RTX cycle. The follow-up data of the remaining 6 patients were evaluated. There was a significant improvement in arthritis of Disease Activity Score of 28 joints - C-reactive protein and Clinical Disease Activity Index compared with baseline. The median change in modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and carbon monoxide diffusing capacity between baseline and 12months were similar. Lung involvement was detected in 5/6 of survivor patients, FVC was improved in 2/5, worsened in 1/5, and remained stable in 2/5 at the end of 1year. Among the 5 diffuse cutaneous SSc patients, none of the patients' mRSS deteriorated by more than 5 points, while one patient's mRSS improved by greater than 5 points. This study suggests that RTX is effective for arthritis in patients with SSc. Also, the effectiveness of RTX in skin and lung involvement of SSc was predominantly toward stable disease or improvement. Despite the long disease duration, the presence of patients who showed improvement in skin and lung involvement after RTX treatment suggests the need to investigate predictors of RTX response.

Chemotherapy casted shadow: Mees' and Beau's lines.

A 28-year-old female received six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy to treat diffuse large B-cell lymphoma. She completed her treatment (see Figure 1) 3 weeks before this photograph. Examination showed multiple white lines on the fingernails, known as Mees’ lines. Mees’ lines are transverse, nonblanching white bands that run parallel to the lunula around the entire nail bed. The lines matched the start of each cycle, with the distance between the lines representing the time interval between cycles. In this patient, four lines can be identified with consistent intervals on the body of her nails, while the fifth and sixth lines are seen at a more significant distance at the nail-free edge. This might be related to treatment delay after cycle 2 (40 days) due to intensive care unit admission with sepsis and coronavirus disease (COVID-19) pneumonia. In the third and fourth cycles (the outer lines on the nail bed), we can see roughness and indentation (on the left-hand thumb and index finger), representing Beau's lines. Beau's lines are transverse depressions in the nail plate caused by transient cell division interruption in the proximal nail matrix. Both lines are commonly seen in patients with a history of chemotherapy exposure. The authors declare they have no conflicts of interest. The photograph was taken with the patient's informed consent and in accordance with the declaration of Helsinki The authors received no specific funding for this work. Informed consent was obtained. The authors declare that the data supporting the findings of this report are available within the article.

Rituximab - Progress but Still Not a Final Resolution for Pemphigus Patients: Clinical Report From a Single Center Study.

Pemphigus is a rare autoimmune disease characterized by the production of pathogenic autoantibodies against desmosomal adhesion proteins, desmoglein 1 and 3. The pathophysiological process leads to the development of blisters and erosions on mucosal and/or skin surfaces as the main clinical manifestation of the disease. Rituximab emerged as the first-line therapeutic option for pemphigus due to its ability to induce remission by depleting peripheral B lymphocytes. Our aim was to assess the efficacy of rituximab in the treatment of patients in Croatia. A single-center, retrospective study was conducted on 19 patients treated with rituximab following a rheumatoid arthritis dosing protocol between October 2015 and March 2021, with a mean follow-up of 24.1 months. After the first rituximab cycle, two patients achieved complete remission off therapy (10.5%), and six patients achieved complete remission on minimal therapy (31.6%). Partial remission was observed among ten patients (52.6%). Eight patients (44.4%) relapsed after the first rituximab cycle. The mean relapse time was 21 months. Seven patients received two rituximab cycles, and three patients received three cycles. Overall, 13 out of 19 patients experienced complete remission at some point during the study, while there were no non-responders after the rituximab treatment. No statistically significant associations were observed between age, sex, type of disease involvement and clinical remission, either on or off therapy. A steady decrease in anti-desmoglein 1 and anti-desmoglein 3 levels was measured among all patients following rituximab treatment. One patient experienced a treatment-related adverse event of infectious etiology (cellulitis). One patient died following the first rituximab cycle, with the cause of death likely not to be associated with the treatment. Rituximab is an effective disease-modifying agent in the treatment of pemphigus with the main benefit of reducing corticosteroid exposure and steroid-related side effects among pemphigus patients. However, a feature of rituximab therapy is high relapse rates and the need for repeated treatment cycles to achieve complete remission. Developing an optimal protocol for rituximab treatment and finding suitable markers for predicting relapse will improve the management of pemphigus patients.

Risk-adapted chemoimmunotherapy using brentuximab vedotin and rituximab in children, adolescents, and young adults with newly diagnosed Hodgkin’s lymphoma: a phase II, non-randomized controlled trial

BackgroundCure rates for Hodgkin’s lymphoma are excellent, but excess short-term and long-term morbidities from treatment remain a concern. Immunotherapy targeting both tumor antigens and the immunosuppressive tumor microenvironment in children,...

P044 Giant cell arteritis in an immunocompromised patient with rheumatoid arthritis

Abstract Background/Aims Giant cell arteritis (GCA) is a common medium-large vessel vasculitis with an approximate incidence of 10 cases per 100,000 people over 50 years old. First line management of GCA is with high dose glucocorticoids followed by steroid sparing agents, namely methotrexate with tocilizumab for resistant cases. Here we describe a patient established on methotrexate for rheumatoid arthritis, receiving rituximab with intravenous methylprednisolone (IVMP) who went on to develop GCA. Methods A 65-year-old Caucasian female with seropositive rheumatoid arthritis (RA) established on 20mg weekly subcutaneous methotrexate and low dose 5mg prednisolone was escalated to her tenth cycle of rituximab with 100mg IVMP for an arthritic flare. The day after her second infusion, two weeks apart, the patient presented with headaches. These were severe temporal pains with scalp tenderness for the past four weeks. She denied visual changes, jaw claudication or polymyalgia rheumatica features. Examination identified bilateral thickened and tender temporal arteries. Ultrasound confirmed bilateral frontal temporal artery halo signs, with intimal thickening of 0.9mm and 0.4mm of the left and right respectively. Blood tests showed a rise in C-reactive protein to 46mg/L from 13mg/L. In view of these findings, procedural risks and recent immunosuppression biopsy was not sought. The patient was commenced on 40mg prednisolone before weaning by 5 mg 2-3 weekly. Her headache improved, without relapse and her CRP normalised within 2 weeks. Given tocilizumab had previously been ineffective in the patient’s RA management, she declined transition to this biologic and her methotrexate was increased to 25mg. Results Development of GCA in a patient with pre-established immunotherapy is rare. This report represents only the second case noted in the literature of the vasculitis occurring in a patient whilst on rituximab. Excluding tocilizumab (anti-IL6), a meta-analysis of other biological agents including infliximab, adalimumab, etanercept (anti-TNF) and abatacept (anti-CTLA4) have not been proven to have clinical significance over placebo in GCA. However, evidence of rituximab and its role in GCA is limited with no clinical trials. Contrary to this case of GCA, rituximab (anti-CD20) therapy has a well-recognised role in ANCA associated vasculitis and there are growing calls for trials in large vessel vasculitides. Recent case series of rituximab in Takayasu’s arteritis have presented contrasting outcomes of persistent disease activity versus clinical and laboratory remission. Robust clinical trials are therefore required to evaluate the long-term impact of rituximab on large vessel vasculitis. Conclusion Although rare, clinicians should be vigilant for the development of GCA despite established immunosuppression. Disclosure N. Chauhan: None. A. Kinder: None.

OA06 Single-centre experience of the use of Rituximab for inflammatory arthritis during the COVID-19 pandemic

Abstract Background/Aims There is increasing evidence from large observational cohort studies that rituximab may result in more severe COVID-19 disease and increase the risk of death. There is also concern that rituximab impairs response to the COVID-19 vaccination. We aimed to determine the outcome of patients with inflammatory arthritis treated with rituximab during the current COVID-19 pandemic. Methods We conducted a single-centre retrospective observational study of patients with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA) treated with rituximab under follow-up in a dedicated clinic from the start of the COVID-19 pandemic in February 2020 until September 2021. We assessed the outcomes of those with COVID-19 infection and serological response to COVID-19 vaccination in patients tested for SARS-CoV-2 Spike antibodies. Results So far, 139 patients have been included (82.0% female, mean age 63.0 [SD 15.6] years). 132 patients had RA and 7 had JIA. 18 patients (12.9%) reported testing positive for COVID-19 infection. Of these, 11 patients (61.1%) were hospitalised. 9 (50%) did not require supplemental oxygen, 2 (11.1%) required supplemental oxygen, 6 (33.3%) required non-invasive ventilation or high-flow oxygen, and 1 (5.6%) required invasive mechanical ventilation. 4 patients (12.2%) died, average number of days from COVID-19 symptom onset to death was 27 (SD 5.2). 8 patients (44.4%) made a full recovery, 6 patients (33.3%) were left with permanent health defects. There was a trend toward higher levels of care in patients who had received more rituximab cycles. Of 21 patients who received both COVID-19 vaccination doses and had COVID-19 serology performed, only 9 patients (42.9%) had positive COVID-19 serology post vaccination. There was a significant difference in the number of days from last infusion to second vaccination dose between those with a positive serological response (median 231.0, IQR [285.0-194.3] days) compared with those with a negative response (median 504.0, IQR [266.0-580.0] days) (p = 0.007, Mann-Whitney U test). Of 3 patients who had not been vaccinated but had previously confirmed COVID-19 infection (positive PCR), only 1 patient had positive COVID-19 serology. Mean duration from positive PCR test to serology test 83.3 (SD 14.4) days. Since February 2020, at least 19 patients (13.7%) paused rituximab or switched to an alternative biologic due to concerns over COVID-19 risk. Of 17 patients that switched, the most common alternative biologics were abatacept (11), baracitinib (3) and sarilumab (2). 5 patients continued rituximab at a reduced dose of 1 gram per cycle. Conclusion Given the potential for an increased risk of severity of COVID-19 infection and reduced response to COVID-19 vaccination in patients treated with rituximab, ‘pausing’ or ‘delaying’ it and use of alternative therapies to maintain disease control should be considered. The risks and benefits need to be carefully considered on a case-by-case basis. Disclosure J. Kimpton: None. C. Bradbury: None. R. Gravell: None. S. Moore: None. P. Buck: None. M. Leandro: Consultancies; ML has received fees for participating in Advisory Board from Genentech. Grants/research support; ML has received research grant from Roche Basel paid directly to employer, University College London.

OA09 Gene expression analysis reveals distinct ancestry-specific profiles associated with response to rituximab in SLE

Abstract Background/Aims SLE patients of European ancestry frequently have milder and more treatment-responsive disease which is poorly explained. Transcriptional signatures are one approach to stratifying SLE which can distinguish by disease activity, autoantibodies and organ involvement but also vary significantly between patients of different ancestry. We developed two interferon-stimulated gene expression scores (IFN-Score-A and IFN-Score-B) that predict clinical outcomes in SLE. Additional modules of differentially expressed genes associated with disease activity have been described but have not been evaluated for association with ancestry or treatment response. Here, we evaluated the association between pre-defined transcriptional scores for these previously described modules, ancestry and response to B cell depletion with rituximab in a multi-ethnic UK cohort with active SLE. Methods Baseline gene expression was evaluated in pre-treatment whole blood using a customised 96-probe Taqman array in 213 patients with active SLE prospectively enrolled in British Isles Lupus Assessment Group (BILAG) Biologics Register on commencing biologic therapy. Interferon status was evaluated using IFN-Score-A and IFN-Score-B as previously described. Gene expression scores representing Plasmablast, Neutrophil, Myeloid and Inflammation-annotated modules were represented by the median expression of 4-16 genes per annotation. Response to first cycle rituximab was evaluable in 110 patients and was defined by BILAG-2004 criteria at 6 months. Results 128 patients were of European ancestry and 85 were of African ancestry, Subcontinental Asian, East Asian or mixed race. Transcriptional signatures differed between ancestral groups. Patients of European ancestry had lower baseline IFN-scores than non-European ancestries. IFN-scores among European patients were highly correlated with Plasmablast (R2=0.32), Neutrophil (R2=0.54), Myeloid (R2=0.72) and Inflammation (R2=0.62) -annotated scores (p < 0.001). Among patients of non-European ancestry the picture was more heterogeneous; IFN-scores showed no correlation with Neutrophil (R2=0.19, p = 0.08) or Plasmablast (R2=0.02, p = 0.83) scores and their correlation with the other annotations was weaker. Overall BILAG response to rituximab was observed in 70/110 (63%) patients. However, transcript-level hierarchical clustering in non-European ancestry patients revealed distinct profiles for response to rituximab. Cluster 1 were IFN-low and were older with lower serological activity and higher glucocorticoid use. Response to rituximab was observed in only 14%. Cluster 2 were IFN-high with low Neutrophil, Myeloid and Inflammation signatures. 42% achieved a BILAG response to rituximab. Cluster 3 showed globally high expression across all transcript annotations and best response rate to rituximab at 84%. Clusters 2 and 3 were clinically and serologically similar. Clusters derived from European ancestry patients were not significantly associated with response to rituximab but were distinguished by renal involvement. Conclusion We describe distinct transcriptional profiles in a multi-ethnic UK SLE cohort. Baseline gene expression, in particular IFN status, stratified response to rituximab among non-European subjects but was not prognostic among European patients. Development of transcriptional biomarkers should account for ancestral variation. Disclosure L. Carter: None. A. Alase: None. Z. Wigston: None. A. Psarras: None. A. Burska: None. M. Md Yusof: Consultancies; YY has provided consultancy to UCB. J.A. Reynolds: None. M. Wittmann: Consultancies; MW has received consultancy fees from Abbvie, Celgene, Janssen, L’Oreal, Novartis and Pfizer. I. Bruce: Consultancies; IB has provided consultancy to AstraZeneca, Eli Lilly, GlaxoSmithKline, ILTOO Pharma, MedImmune, Merck Serono. Grants/research support; IB has received research funding from Genzyme Sanofi & GlaxoSmithKline. E.M. Vital: Consultancies; MEV has provided Consultancies to Genentech, AstraZeneca, Aurinia, Lilly and Modus Therapeutics. Grants/research support; EMV has received research funding from Astra Zeneca and Sandoz.

P245 Identifying predictors of short-term response to rituximab in extra-glandular primary Sjogren’s Syndrome

Abstract Background/Aims Randomised controlled trials (RCTs) of rituximab (RTX) in primary Sjogren’s syndrome (pSS) have failed to alleviate glandular symptoms and fatigue. The question remains as to whether B-cell depleting therapies have a place for the treatment of pSS. Post-hoc analyses from RCTs showed greater improvement in objective measures such as salivary flow rate, salivary gland ultrasound and histology scores in RTX-treated group vs placebo. Moreover, there are limited data on efficacy of the initial and repeat cycles of RTX on extra-glandular pSS. Here, our objectives were to assess the effectiveness of RTX on extra-glandular symptoms and identify predictors of short-term response with a view to personalised B-cell depleting therapy in pSS. Methods A retrospective longitudinal cohort study was conducted in 40 consecutive RTX-treated pSS patients in a single-centre for over 15 years. All patients fulfilled the 2002 AEG criteria and were CCP negative. Clinical response at 6 months was defined as ≥ 3 point reduction of ESSDAI from baseline. B-cell subsets were measured using highly sensitive flow cytometry. Predictors of short-term response were analysed using penalised logistic regression. Results 38/40 (95%) patients were female, mean (SD) age 54 (13.7) years, median (IQR) disease duration 5 (2-9) years, 39/40 (98%) had positive ANA and 28/40 (70%) were on concomitant immunosuppressant (IS). Mean (SD) ESSDAI at RTX initiation was 11.5 (6.7) and main domains for RTX were articular (73%), skin (23%), haematological (18%), PNS (15%) and lungs (10%). 169 RTX cycles were administered with a total follow-up of 165PY. In Cycle 1 (C1) RTX, the proportion of patient achieving ESSDAI response from baseline was 29/40 (73%; 95% CI 58-87). There were significant reductions in ESSDAI, daily prednisolone dose and IgG levels at 6 months (all p < 0.05). Of C1 responders, 23/29 received retreatment on clinical relapse; of which 8/23 (35%) lost response [secondary non-depletion non-response (2NDNR) associated with anti-RTX antibodies as we previously observed in SLE=4 (17%)]; side effects=1; ineffective=3. Of C1 non-responders, 9/11 were retreated but only 2/9 responded in C2. Overall, 13/40 (33%) discontinued RTX within two cycles. In multivariable analysis, concomitant immunosuppressant [OR 0.07 (95% CI 0.01-0.52); p = 0.010] and achieving compete B-cell depletion in C1 [0.04 (0.02-0.82); 0.036] reduced non-response to RTX. Conclusion All patients with pSS should be co-prescribed immunosuppressant with RTX and future therapeutics should aim to achieve complete depletion. About one in six pSS patients lose response in repeat cycles which is associated with 2NDNR phenomenon. The use of humanised or next-generation type 2 anti-CD20 antibodies should overcome these issues and improve the clinical response of extra-glandular pSS. Disclosure S. Pepple: None. J. Arnold: None. E. M Vital: Consultancies; Dr Vital has received consulting fees from Roche. Grants/research support; Dr Vital has received funding for research from Roche. A. C Rawstron: None. C. Pease: None. S. Dass: None. P. Emery: Consultancies; Prof Emery has received consulting fees from Roche. Grants/research support; Prof Emery has received funding for research from Roche. M. Md Yusof: None.

P241 Efficacy of obinutuzumab in systemic lupus erythematosus patients with secondary non response to rituximab

Abstract Background/Aims Rituximab is a chimeric type-1 anti-CD20 monoclonal antibody approved by NHS England for refractory SLE. Secondary inefficacy with infusion reactions and anti-rituximab-antibodies occurs in 14% of re-treated patients. Obinutuzumab is a next-generation humanised type-2 anti-CD20 antibody licensed for the treatment of haematological malignancies. Methods We collated data from nine SLE patients receiving off-label obinutuzumab for secondary non-response to rituximab with infusion reactions across six centres (Leeds, Bradford, York, UCL, Birmingham and Nottingham). Disease activity was assessed using BILAG-2004 and SLEDAI-2K and serology in local diagnostic laboratories before, and 6 months after, obinutuzumab 2x1000mg infusions 2 weeks apart alongside methylprednisolone 100mg. Results All patients received concomitant oral immunosuppression and prednisolone. 6/9 received hydroxychloroquine. The median number of rituximab cycles before obinutuzumab therapy was 2.5. Before obinutuzumab 6/9 patients had BILAG A/B mucocutaneous, 6/9 had BILAG A/B musculoskeletal and 4/9 had BILAG A/B renal. 6 months after obinutuzumab 1/9 patients had BILAG B mucocutaneous, no patients had BILAG A/B musculoskeletal and 2/9 patients had BILAG A/B renal. Median dsDNA reduced from 118 to 83 IU/mL, C3 increased from 0.53 to 1.02g/L and C4 increased from 0.095 to 0.23g/L. Prednisolone dose was reduced in 5/9 patients; before obinutuzumab all patients received 10mg or more. After obinutuzumab, 4/9 patients received 5mg and were in Lupus Low Disease Activity State (LLDAS). Patient 5 did not respond and required further methylprednisolone and cyclophosphamide at 4 months. Patient 6 had a partial renal response but required renal transplantation, which was successful. Patient 8 responded well to obinutuzumab but died from severe COVID-19 infection (unvaccinated). After obinutuzumab 6 patients with B-cell data all achieved complete depletion including 4/4 assessed with highly sensitive assays. Conclusion These results demonstrate obinutuzumab’s efficacy in patients with secondary non-response to rituximab. These patients have severe disease with few treatment options, but previous responsiveness to B-cell depletion. Therefore, switching to another therapy in this class is mechanistically logical. Obinutuzumab appeared effective in renal and non-renal SLE as well as steroid-sparing. Immunological markers also improved. Obinutuzumab was generally well tolerated and will be further investigated for treatment-refractory lupus in the REGENCY and ALLEGORY trials. Disclosure J.E. Arnold: None. S. Dass: Consultancies; Received consultancy fees from Roche, Abbvie, UCB & Chugai. Honoraria; Received honoraria from Roche, Abbvie, UCB & Chugai. S. Twigg: None. C.H. Jones: None. B. Rhodes: None. P. Hewins: None. M. Chakravorty: None. P. Courtney: None. M. Ehrenstein: Honoraria; Received honoraria from GSK. Grants/research support; Received funding from GSK. M. Md Yusof: None. E. Vital: Consultancies; Received consulting fees from Roche, GSK, Eli Lilly and AstraZeneca. Honoraria; Received honoraria from Roche, GSK, Eli Lilly and AstraZenec. Grants/research support; Received research support from Roche and AstraZeneca (Paid to the University of Leeds).

Simple headache revealed a rare lymphoma: Waldenstrom macroglobulinemia with unique markers: a case report and review of the literature

BackgroundWaldenstrom macroglobulinemia (WM) is a rare lymphoma with an incidence rate of 3 per million people per year, with approximately 1000 to 1500 new cases diagnosed each year in the USA. It is primarily seen in Caucasian males with a median age of 70 years old. Patients are most often asymptomatic, but WM can manifest itself with constitutional symptoms such as lethargy, bleeding, organomegaly, and neurological or fundoscopic abnormalities. WM is characterized by immunoglobulin M (IgM) monoclonal gammopathy, lymphocytic infiltration of bone marrow, and normocytic anemia due to bone marrow replacement.Case presentationOur patient is a Hispanic 67-year-old female that presents with one month of intermittent band-like bilateral headache accompanied by dizziness, light-headedness, nausea, and blurred vision. A thorough diagnostic workup was performed, including serum protein electrophoresis (SPEP) with serum immunofixation (SIFE) showing an M spike and IgM kappa. Bone marrow biopsy was significant for lymphoplasmacytic infiltration with nodular B cells (CD19+, CD20+, CD22+). Computerized Tomography (CT) imaging showed splenomegaly in the patient. Treatment was provided for hyperviscosity syndrome with plasmapheresis twice. The patient reported improvement of her symptoms and was then scheduled for chemotherapy. Throughout 7 months, our patient received multiple cycles of bortezomib, dexamethasone, and rituximab. While her symptoms improved her psychiatric status got progressively worse.ConclusionIt is important not to neglect symptoms such as a headache, which may seem small, but could serve as a clue in the diagnosis of Waldenstrom's macroglobulinemia.

Early rituximab treatment is associated with increased and sustained remission in pemphigus patients: A retrospective cohort of 99 patients.

Rituximab is the front-line therapy for pemphigus disease. Although very effective, relapse rates are high. We assessed factors associated with disease remission and early relapse following the first rituximab cycle. A single center, retrospective cohort study of patients with pemphigus treated with rituximab (1000 mg0, 14 days) at the Autoimmune Bullous Disease Clinic of the Division of Dermatology in Rabin Medical Center, Israel, between January 1, 1995 and March 31, 2020. The cohort included 99 patients with a median follow-up of 37 months (range 12-155). After a single rituximab cycle, 74 patients (75%) achieved remission. Increased time to rituximab was associated with decreased remission rates (OR, 0.98 per month; 95% CI, 0.97-0.998). Of patients in remission with sufficient follow-up, 15/69 (22%) experienced an early relapse (≤12 months from remission). Prolonged time to rituximab and increased baseline disease severity, were associated with early relapse (OR, 1.02 per month; 95% CI, 1.001-1.04; OR, 1.04 per point; 95% CI, 1.01-1.08, accordingly). Initiating rituximab early following diagnosis is recommended. Maintenance rituximab infusions, especially for patients with severe baseline disease, should be further investigated.

Rituximab treatment in pediatric patients with steroid-dependent nephrotic syndrome: A tertiary hospital

BackgroundCorticosteroids have had a central role in the treatment of nephrotic syndrome. The management of these patients who become dependent to steroids is complex, involving different immunosuppressive drugs patterns. The monoclonal antibody anti CD20, Rituximab, is likely to have beneficial effects in cases of steroid-dependent nephrotic syndrome patients with no easy resolution, even when we cannot make a statement about the specific role in the impact. We bring our personal experience in pediatric patients treated with this medication during the last years, to provide a thorough overview and useful information about the role of Rituximab in this pathology. MethodsRetrospective study in patients with steroid-dependent idiopathic nephrotic syndrome controlled in the division of Pediatric Nephrology of a Spanish tertiary hospital in those patients who had received at least one treatment cycle of Rituximab, at any moment along the evolution of the disease. ResultsThe study involved 8 patients. All of them previously received immunosuppressive therapy. The Rituximab were administered as an intravenous infusion, in a dose of 375 mg/m2, and all doses were administered in a period during which the disease was in remission. The depletion of lymphocytes B (CD19, 0%) were confirmed after the first dose of Rituximab except for one, with a lymphocyte count of 1%. The period of depletion lasts 10,3 months (median; range 6,5–16 months), and only one of the patients registered a relapse of the disease in this period. A reduction of relapses suffered by patients has been shown after the treatment began (3,6 relapses/year in the previous year to the start of the treatment versus 0,1 relapses/year during the first year post-rituximab). The relapse-free survival in the first year reached 83,3% in patients who suffered more than one relapse (75% of patients), and without a relapse after the treatment began in 2 cases. One or more drugs could be removed in 87,5% of patients after the first cycle of rituximab. After the rituximab treatment, we reached a 96,5% decrease in the corticosteroids doses administered (28,5 mg/m2/day during the 3 months pre-treatment versus 1 mg/m2/day in the last 3 months of patient monitoring). Not a significant observed adverse effect attributed to the drug after the post-rituximab monitoring period (median 46,5 months, range 5–97 months). ConclusionThe favorable results reported after rituximab treatment in our patients seems to confirm the effectiveness of this drug in the steroid-dependent nephrotic syndrome, making that therapeutic option into consideration and legitimating the use of the drug in complex cases involving pediatric patients. Even so, it seems recommendable to design pertinent studies to clarify, among others, the optimum regimen of the treatment (dose, interval and cycles), clinical repercussion and potential adverse effects in long terms.

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

BackgroundDiffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody–drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells.MethodsWe conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety.ResultsOverall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P=0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P=0.75). The safety profile was similar in the two groups.ConclusionsAmong patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann–La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.)

Successful treatment with rituximab in a patient with lupus cerebritis and posterior reversible encephalopathy syndrome: a case report

Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) has a diverse and broad spectrum of severity and prognosis, with some devastating manifestations. However, its diagnosis and treatment remain unclear and controversial. Case Report: A 19-year-old woman with SLE presented with fever, headache, quadriparesis, and tremor. Brain magnetic resonance imaging (MRI) showed sulcal enhancement in the cortical sulcus, and intravenous methylprednisolone (500 mg/day) and immunoglobulin (2 g/kg for 5 days) were started under the suspicion of aseptic lupus meningitis. However, the patient’s neurologic symptoms worsened; brain MRI showed a newly developed brain parenchymal lesion, suggesting lupus cerebritis and posterior reversible encephalopathy syndrome. Two cycles of rituximab (850 mg/day, 1-week interval) were administered for the treatment of refractory NPSLE. Her neurologic symptoms gradually improved after the second cycle, and she was discharged with minimal neurologic symptoms. Conclusion: Rituximab may be a therapeutic option for refractory lupus cerebritis. Further research is needed to accurately determine its efficacy.

Recent Clinical Trials Insights into the Treatment of Primary Membranous Nephropathy.

Immunosuppressive therapy is mandatory for primary membranous nephropathy with persistent nephrotic proteinuria or anti-phospholipase A2 receptor antibodies, reduced kidney function, or another risk factor for progression. Rituximab has demonstrated efficacy for proteinuria remission compared with renin-angiotensin system blockade or cyclosporine in two well-powered randomized controlled trials. More recently, STARMEN showed that alternating glucocorticoid-cyclophosphamide is superior to sequential tacrolimus-rituximab for proteinuria remission, although it was associated with a higher risk of non-serious adverse events. However, sequential tacrolimus-rituximab involved delayed lower dose rituximab and was the worst-performing rituximab regimen among those tested in randomized clinical trials. The RI-CYCLO pilot study did not demonstrate superiority of glucocorticoid-cyclophosphamide over rituximab and found no difference in adverse events. Overall, STARMEN and RI-CYCLO confirmed the efficacy of glucocorticoid-cyclophosphamide in patients with high-risk membranous nephropathy and the role of rituximab as a valid alternative. However, none of the trials tested an optimized rituximab protocol involving a second rituximab cycle before declaring treatment failure. Calcineurin inhibitors should be considered third-line drugs and sequential use of calcineurin inhibitor rituximab did not add over rituximab-only regimens. We critically review recent randomized controlled trials, propose a research agenda, and call for multinational pragmatic trials that enroll patients at referral centers to address unmet research needs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40265-021-01656-1.

Multiple cycles of rituximab therapy for pemphigus: A group of patients with difficult- to-treat disease or a consequence of late rituximab initiation?

Pemphigus is a serious autoimmune disease with few appropriate therapeutic options. Although rituximab (RTX) has recently shown great promise in this regard, the best protocol of its administration is remains to be elucidated. This study aimed to evaluate the patients who need at least 3 cycles of treatment with RTX to identify hard-to-treat patients' characteristics, which might lead to consider more prompt protocols for treatment of them. A retrospective cross-sectional study was conducted on 45 patients with pemphigus vulgaris who received at least 3 cycles of RTX. Their demographic, clinical, and laboratory data as well as details of treatment protocol and final clinical situation of patients were evaluated. Totally, 45 patients (21 men and 24 women) with mean age of 44.33 years were included in this paper. Women were about 8 years older than men (mean age: 48.1 years versus 40.1 years, p: 0.011) and needed RTX approximately 2 years later in their course of disease (gap: 41.04 months vs. 14.85 months, p: 0.003). Buccal, truncal, and scalp regions were the most frequent sites of involvement respectively. A significant decrease in both anti-Dsg1, 3 was seen at last visit compared to baseline. However, the amount of this decrement was not significantly different between them (p: 0.083). Partial remission in 31.11%, complete remission in 24.44%, relapse in 15.56%, partial remission on treatment in 15.56% and complete remission on treatment in 13.33% were seen at the last follow-up session. RTX is an effective medication for PV even in patients with refractory disease and its therapeutic effect is increased with each subsequent cycle. Male gender, severe oral mucosal involvement on disease onset and extensive scalp and truncal lesions as first cutaneous manifestation of disease are more likely to be signs of refractory PV. Hence, it is reasonable to consider more prompt protocols for treatment of these cases. Moreover, late prescription of RTX during the course of disease might play a role in presence of more resistant form of disease.

A novel rituximab administration protocol to minimize infusion-related adverse reactions in patients with B-cell lymphoma.

Background Infusion-related reactions (IRRs) during rituximab administration are occasionally severe and remain problematic in oncology practice. Aim To establish a safer, risk-stratified rituximab protocol for patients with B-cell lymphoma. Method We stratified patients into low-, moderate-, and high-risk groups according to the number of risk factors for IRRs, specifically, low-grade histology and bulky tumors (>10cm): Then, the administrating schedule of rituximab (375mg/m2, diluted in 1mg/mL concentration) was individualized. For the first rituximab cycle, the low- and moderate-risk groups underwent conventional infusion #1 (25-200mg/h, ~4.3h), and the high-risk group underwent long infusion (25-100mg/h, 6.8h). Patients in the low-, moderate-, and high-risk groups without IRRs in the first cycle underwent short infusion (100-400mg/h, 2.3h), conventional infusion #2 (100-200mg/h, 3.5h), and conventional infusion #1, respectively. Patients with IRRs in the first cycle received a second rituximab cycle with the same schedule as the first cycle. The procedure for the third cycle was at the attending physician's discretion. Results Among 81 patients, the overall incidence of IRRs was 28%. IRR incidences in the low- (n = 39), moderate- (n = 35), and high-risk groups (n = 7) were 31%, 20%, and 57%, respectively. All IRRs were grade ≤2. The overall conversion rate to short infusion in the third cycle was 54%, without any IRRs. Conclusions Our step-by-step rituximab protocol demonstrated a fewer incidence of severe IRRs among B-cell lymphoma patients receiving rituximab.

The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma

The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma

CTNI-57. MATRix REGIMEN FOR NEWLY DIAGNOSED PRIMARY DIFFUSE B-CELL LYMPHOMA OF THE CENTRAL NERVOUS SYSTEM

Abstract We report our experience treating 20 patients with newly diagnosed primary diffuse B-cell lymphoma of the central nervous system with the MATRix regimen as reported by Ferreri, et al in 2016. The median age was 65 y; 8 patients were men and 12 were women. Eighteen had cerebral mass lesions, 1 had a paraspinal mass, and 1 leptomeningeal disease. Treatment consisted of 4 cycles of rituximab 375 mg/sq m (Days 1, 6); methotrexate 3.5 g/sq m (Day 2); cytarabine 2 g/sq m every 12 h (Days 3, 4); and thiotepa 30 mg/sq m (Day 5). Patients without disease progression received carmustine 400 mg/sq m and thiotepa 5 mg/kg followed by autologous bone marrow transplantation. Four patients were switched to MATRix after 6 cycles of methotrexate and rituximab and received only 2 initial cycles including cytarabine and thiotepa. Overall, 14 patients completed initial chemotherapy. Twelve of these 14 went on to transplantation; one patient had early disease progression, and in one no stem cells could be collected. All 4 patients over 70 y died early after 1-2 cycles; the median age of these was 80 y, and the causes of early death were neutropenic fever, septic thrombophlebitis, and cardiac arrest. One patient who completed the entire regimen including transplantation died of fungal pneumonia; the other 13 experienced no serious acute toxicity. One patient had late disease progression; one developed symptomatic leukoencephalopathy. Thirteen of the 20 patients remain alive. Median OS for the cohort is 698 days. These preliminary data suggest that the MATRix regimen in safe and highly effective in the newly diagnosed setting. However, the high incidence of early death in patients over 70 y suggests that the regimen may be too toxic for elderly individuals.

Small Lymphocytic Lymphoma Presenting as a Breast Lump: A Rare Presentation of Non-Hodgkin's Lymphoma

Approximately one-fourth of non-Hodgkin's lymphomas (NHLs) present with an extranodal origin. Primary and secondary involvements of the breast by lymphoma are rare because of the paucity of lymphoid tissue in the breast. Primary breast small lymphocytic lymphoma (SLL) typically presents as a manifestation of widespread chronic lymphocytic leukemia (CLL). A 58-year-old female presented to our clinic with a palpable breast mass. She had no cytopenias and her absolute peripheral B lymphocyte count was less than 5000/microL. The mass was biopsied and histology with immunohistochemistry showed neoplastic cells positive for CD23 and CD5 confirming the diagnosis of small B cell lymphocytic lymphoma of the breast. Further imaging revealed extensive mediastinal and retroperitoneal lymphadenopathy. Histopathology of bone marrow biopsy revealed diffuse infiltration with SLL. The patient was treated with six cycles of fludarabine, cyclophosphamide and rituximab (FCR) with excellent clinical response. To our knowledge, this is the first case of SLL infiltration of the breast without CLL treated successfully with FCR.