Efficacy Of Rituximab Research Articles

β-Sitosterol Inhibits Tumor Growth and Amplifies Rituximab Sensitivity through Acid Sphingomyelinase/Ceramide Signaling in Diffuse Large B-Cell Lymphoma.

Rituximab (RTX) resistance is a notable challenge in treating diffuse large B-cell lymphoma (DLBCL). β-Sitosterol (β-ST) is a plant sterol that has been found in a broad variety of fruits, spices, and medicinal plants. The antineoplastic properties of β-ST are established in various solid malignancies; however, its effect on DLBCL is uncharted. This study investigates the role of β-ST in DLBCL as well as the underlying mechanisms. Our findings indicated that β-ST impeded DLBCL cell proliferation in a concentration- and time-dependent manner. β-ST appeared to alter sphingolipid metabolism, facilitate acid sphingomyelinase (ASM) translocation to the plasma membrane, augment ceramide platforms through increased ceramide synthesis, and consequently induce apoptosis in DLBCL cells. Furthermore, we found that RTX initiated both apoptotic and survival pathways in vitro, with the former contingent on the transient activation of the ASM, and β-ST could amplify the anti-DLBCL efficacy of RTX by modulating ASM/Ceramide (Cer) signaling. Collectively, our findings elucidate the mechanistic role of β-ST in DLBCL and underscore its potential in amplifying the antineoplastic efficacy of RTX via ASM activation, proposing a potential avenue to improve the efficacy of RTX therapy.

Efficacy of thrombopoietin receptor agonists versus rituximab in non-responsive immune thrombocytopenia-A single centre retrospective analysis.

Management of immune thrombocytopenia (ITP) beyond initial glucocorticoid therapy is challenging. In this retrospective single-centre cohort study, we compared all ITP patients relapsed or non-responsive to glucocorticoid therapy treated with either continuous TPO-RAs (n = 35) or rituximab induction (n = 20) between 2015 and 2022. While both groups showed high initial complete response rates (CR, 68.6 vs. 80.0%, ns), the overall rate of progression to the next therapy was higher after time-limited rituximab (75.0 vs. 42.9%), resulting in a lower relapse-free survival (median 16.6 vs. 25.8 months, log-rank; p < 0.05). We conclude that both treatments show similar initial efficacy and their ideal duration of therapy warrants further investigation.

Combination therapy of targeting CD20 antibody and immune checkpoint inhibitor may be a breakthrough in the treatment of B-cell lymphoma

BackgroundCD20 is a membrane protein extensively expressed on the surface of B cells at various stages of development and differentiation. Herein, we conducted a bibliometrics analysis of the literature on CD20-targeting antibody therapy in lymphoma. MethodsA total of 6663 articles were downloaded from the web of science core collection (WOSCC) from 1999 to July 23, 2022. Bibliometric.com was used for citation and annual publications analysis. VOSviewer was used to map countries/institutions/authors/journals nodes and links, extract hotspot keywords, and analyze the time trend of keywords. Citespace was employed to recognize the turning points based on the centrality value of countries, define the topic distribution of academics according to the map of dual-map overlay of journals, and characterize the emerging topics or landmark articles in a field based on references citation bursts. ResultsAll articles were cited 225,032 times, averaging 33.77. The number of articles increased from 1999 to 2002, while the growth rate entered the platform after 2002. The USA was the most publication country, and China was the largest emerging country. Hotspots in this field still focus on the efficacy of rituximab in treating non-Hodgkin's lymphoma and the pathogenesis of lymphoma Application of generation CD-20 antibodies or molecule inhibitors in clinical research and cellular therapy/immunotherapy, such as CAR-T and PDL1/PD1 were the emerging research topics. ConclusionThis study provides essential information and the tendency of the CD20-targeting antibody therapy in lymphoma by using bibliometric and visual methods, which would provide helpful references for clinical experiments and basic scientific research.

A systematic review on the efficacy of the biologic therapies Rituximab, Belimumab and Anifrolumab in Lupus Erythematosus

A systematic review on the efficacy of the biologic therapies Rituximab, Belimumab and Anifrolumab in Lupus Erythematosus

Study protocol for a randomised, phase II, double-blind, experimental medicine study of obinutuzumab versus rituximab in ANCA-associated vasculitis: ObiVas

IntroductionRelapses in ANCA-associated vasculitis (AAV) increase the incidence of end-organ damage and their prevention requires prolonged immunosuppressive therapy. Rituximab, a type I anti-CD20 B cell depleting monoclonal antibody, is the...

The successful use of rituximab in IgA nephropathy patients with podocytopathy: a case series.

Immunoglobulin A nephropathy (IgAN) with podocytopathy is a rare pathological type of glomerular disease. The use of rituximab (RTX) in the treatment of glomerular diseases has increased in recent decades, but the efficacy of RTX in the treatment of patients with IgAN and podocytopathy has rarely been reported. This was a single-centre retrospective study of IgAN patients with podocytopathy who were treated with RTX as second-line therapy was conducted at our centre from 2019 to 2022. The aim of this study was to investigate the efficacy and safety of RTX in IgAN patients with podocytopathy. Seven out of eight patients met the criteria for complete remission following RTX therapy. Only one patient experienced adverse events (infectious diarrhoea and pulmonary infection) and experienced relapse 6 months after RTX therapy. The maximum relapse-free time after RTX therapy was 20 months, while the maximum relapse-free time before RTX therapy was only 6 months. The number of relapses before RTX therapy (per year) was one to four; moreover, seven patients did not relapse and maintained remission at the last follow-up despite steroid withdrawal after RTX therapy. Overall, RTX effectively reduced proteinuria, increased the maximum relapse-free time, reduced the number of relapses per year and helped patients stop steroid use as soon as possible. RTX also helped most patients achieve clinical remission. RTX appears to be an effective and safe alternative for treating IgAN patients with podocytopathy with steroid dependence or frequent relapse.

Rituximab as a Therapeutic Strategy in Hemophagocytic Lymphohistiocytosis: Efficacy, Outcomes, and Survival-Insights From a Systematic Review.

Hemophagocytic lymphohistiocytosis (HLH) is a severe immunologic disorder that can be fatal if left untreated. The condition is characterized by excessive immune system activation and is often triggered by infections such as Epstein-Barr virus (EBV). Rituximab, an anti-CD20 monoclonal antibody, has been suggested as a treatment, particularly for EBV-associated HLH. A systematic review was conducted using PRISMA guidelines, with a literature search spanning PubMed, Scopus, Web of Science, and the Cochrane Library. The inclusion criteria focused on studies that assessed rituximab's efficacy in treating HLH. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. Of 783 identified records, 24 studies were included in the final analysis. Rituximab was typically administered at 375mg/m2, with varying doses and treatment frequency. Clinical response, often seen within 1 month, was assessed by improvements in clinical symptoms and laboratory findings. Survival rates posttreatment displayed a wide range, with instances of complete remission and disease-free periods, as well as reports of relapse and mortality. Rituximab demonstrates the potential for significant clinical benefit in treating HLH, particularly when associated with EBV, showing promise in reducing disease activity and contributing to remission. These findings encourage further research and clinical trials to refine the therapeutic protocols and better understand the long-term effects of rituximab in HLH management.

Efficacy of rituximab-containing regimens used as first-line and rescue therapy for giant cell hepatitis with autoimmune hemolytic anemia a retrospective study

ObjectiveTo evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA). MethodsThis retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR. The secondary outcomes included relapses and adverse events. ResultsTwenty patients (8 females and 12 males; age range 1–26 months), 15 receiving conventional regimens and 5 receiving RTX-containing regimens, were included. The CR rates were 73.3 % (11/15) and 100 % (5/5) in the conventional and RTX-containing groups, respectively. The time-period required for CR was significantly shorter in the RTX-containing group than in the conventional group (6 (3–8) versus 14 (5–25) months, P = 0.015). Relapses occurred in 30.8 % (4/13) of patients in the conventional group; all achieved CR after adding RTX. Relapses occurred in 40.0 % (2/5) of patients in the RTX-containing group; both achieved CR after adding intravenous immune globulins or tacrolimus. Transient low immunoglobulin and infections were recorded in both groups. Treatment withdrawal was achieved in 73.3 % (11/15) and 60.0 % (3/5) of patients receiving conventional and RTX-containing regimens after 36 (2–101) and 22 (4–41) months, respectively. Two patients in conventional group died of disease progression and infection. ConclusionsRTX-containing first-line therapy achieves CR of GCH-AHA more quickly than the conventional therapy. RTX is efficacious when added to rescue therapy.

Efficacy and safety of outpatient fludarabine, cyclophosphamide, and rituximab based allogeneic hematopoietic cell transplantation in adults with severe aplastic anemia

The age effect in severe aplastic anemia (SAA) following allogeneic hematopoietic cell transplantation (HCT) favors the use of reduced intensity conditioning (RIC) regimens in older adults. We implemented a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and rituximab (FCR) to improve HCT outcomes in SAA. Patients who underwent first HCT for SAA utilizing an FCR regimen between January 2016 and May 2022 were included. Outcomes analyzed included time to engraftment, incidence of graft failure, GVHD, viral reactivation, disease recurrence, and GVHD-free, relapse-free survival (GRFS). Among 24 patients included, median age was 43.5 years (22–62) and a variety of donor types and stem cell sources were represented. At median follow-up of 26.9 months (2.4–72.7), no cases of grade III-IV acute (aGVHD) or severe chronic GVHD (cGVHD) were recorded. Viral reactivation was minimal, and there were no cases of graft failure or PTLD, with 100% disease-free and overall survival at last follow up. The estimate of 1-year GRFS was 86.3% (95% CI: 72.8–100%), with moderate cGVHD accounting for all events. The FCR regimen in SAA was well tolerated, even in older adults, with 100% disease-free survival with low GVHD and infection rates. These encouraging findings should be validated in larger prospective trials.

The emergence of circulating activated autoreactive desmoglein 3-specific follicular regulatory T cells is associated with long-term efficacy of rituximab in patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is characterized by autoantibodies targeting keratinocyte adhesion proteins desmoglein (Dsg) 1 and 3, and by the human leukocyte antigen (HLA) predisposition allele HLA-DRB1*0402. Treatment using rituximab (RTX) combined with short-term corticosteroids (CS) allows disease control and long-lasting remission. The principal aim of this study was to evaluate the impact of RTX on the circulating subpopulations of Dsg3-specific T lymphocytes that specifically regulate B-cell responses: follicular helper T (Tfh) and follicular regulatory T (Tfr) lymphocytes. Using the HLA-DRB1*0402 tetramer loaded with the Dsg3 immunodominant peptide, we used flow cytometry to analyse the frequency, polarization and activation status of blood Dsg3-specific follicular T-cell populations at baseline, month (M) 6 and long-term follow-up (M60-90) from patients with PV. At baseline, we observed a predominance of Tfh1* and Tfh17 subsets and an underrepresentation of the Tfh2 subset among autoreactive Dsg3-specific Tfh cells compared with nonautoreactive Tfh cells. RTX treatment induced a decrease of autoreactive Tfh cells with no effect on their polarization during follow-up. In parallel, we observed the emergence of a Dsg3-specific Tfr subpopulation with a significant overexpression of the surface activation markers PD1, ICOS and CD25 that was not observed at the surface of autoreactive Tfh and nonautoreactive Tfr cells of the same patients with PV. In contrast, very few Dsg3-specific Tfr cells were observed in patients with PV who were treated with CS alone. Here we show that the emergence of circulating autoreactive Dsg3-specific Tfr cells is associated with the long-term efficacy of RTX in patients with PV.

Relapse during and after regular single-dose rituximab treatment in adult patients with steroid-dependent nephrotic syndrome.

Rituximab is widely used in patients with steroid-dependent nephrotic syndrome. However, information on the effect of long-term rituximab treatment is limited. This study examined the efficacy of rituximab during and after treatment in adult patients with steroid-dependent nephrotic syndrome. This retrospective cohort study included 30 patients with steroid-dependent nephrotic syndrome. Patients received regular single-dose rituximab (500mg) intravenously every 6months. Discontinuation of rituximab was considered after four to six doses if there was no recurrence of nephrotic syndrome. Glucocorticoid discontinuation with remission, first relapse after rituximab initiation, and relapse after regular rituximab treatment discontinuation were evaluated. The median age was 38 (range 18-67) years. Of 30 patients, 13 and 17 were men and women, respectively. Prior to rituximab treatment, the median number of nephrotic syndrome relapses in the patients was 5 (range 2- > 20). The 1year discontinuation rate of glucocorticoids with remission was 83%. All patients discontinued glucocorticoid treatment at least once until 3years and 7months. The 1 and 2year relapse rates after initiation of rituximab treatment were 0% and 3%, respectively. 25 patients discontinued regular rituximab treatment after a median number of six (4-12) doses. Six patients relapsed after discontinuing rituximab, and the 1 and 2year relapse rates after the last regular rituximab treatment were 9% and 25%, respectively. All patients with steroid-dependent nephrotic syndrome who received rituximab could discontinue glucocorticoid treatment with remission, and three-fourths of the patients remained in remission for > 2years after discontinuing rituximab treatment.

Frontline treatment with zanubrutinib plus rituximab (ZR) followed by short course R-DHAOx in patients with mantle cell lymphoma (MCL): Results of the phase II CHESS clinical trial.

7062 Background: Combining Bruton’s tyrosine kinase (BTK) inhibitor and rituximab showed favourable efficacy as first-line therapy for mantle cell lymphoma (MCL). Zanubrutinib, a next-generation, highly-selective BTK inhibitor, achieved promising antitumor activity in MCL. In this multicenter phase II trial (CHESS - chemo-less), we aimed to investigate the efficacy and toxicity of zanubrutinib plus rituximab (ZR) combination, followed by short course cytarabine-based chemotherapy, then zanubrutinib maintenance as frontline therapy for MCL (NCT04624958). Methods: Previously untreated MCL patients enrolled and received induction therapy of ZR until complete response (CR) or to a maximum of 12 cycles, and followed by 4 cycles of R-DHAOx regimen (rituximab, dexamethasone, cytarabine and oxaliplatin). Patients achieving CR after chemotherapy would receive maintenance therapy with zanubrutinib for a maximum of 1 year. The primary endpoint was CR rate after induction therapy with ZR regimen. Minimal residual disease (MRD) of bone marrow and peripheral blood were evaluated by flow cytometry. Results: From Oct 2020 to Nov 2023, a total of 42 patients were enrolled and the enrollment was finished. The median age was 57 years (IQR, 51-64). Stage III-IV accounted for 92.8%, and 42.8% were intermediate or high risk simplified MIPI. Thirty-four patients (81.0%) were classic histological subtype. The median cycle of ZR was 4 (range, 2-6). As of Jan 2024, among 37/42 patients with post-treatment PET evaluation, the best CR rate of ZR regimen was 91.9% (34/37), and 94.1% (32/34) obtained CR after 2-4 cycles. The bone marrow MRD negative CR rate was 92.0% (23/25). The other 5/42 patients were still receiving ZR treatment, and PET evaluation would be performed subsequently. Among 27 patients who finished chemotherapy and were evaluable for response, only one patient experienced disease progression. With a median follow up of 11.6 months, the 1-year progression-free survival and overall survival was 90.1% and 96.7%, respectively. Two patients died due to lymphoma (n=1) and COVID-19 (n=1). Grade 3-4 adverse events on ZR regimen were neutropenia (n=3), fatigue (n=2), and aminotransferase (n=1). During chemotherapy, grade 3-4 thrombocytopenia was observed in 75.8% of patients. Conclusions: Induction treatment with ZR followed by short-course R-DHAOx chemotherapy yielded promising antitumor efficacy. This strategy might reduce the toxicity of cytarabine-based chemotherapy without weakening the therapeutic efficacy. Clinical trial information: NCT04624958 . [Table: see text]

A Retrospective Study of R±DHAX Regimen versus R-CHOP Regimen First-Line Treatment of Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed, and they were divided into rituximab±DHAX (R±DHAX) regimen group (18 cases) and rituximab±CHOP (R-CHOP) regimen group (18 cases) according to the treatment plan, and clinical features, efficacy and survival of the patients were observed. Compared with R-CHOP group, patients of the R±DHAX group were older, and had worse performance status and higher IPI score, the differences between two groups in age, ECOG score and IPI score were statistically significant ( P =0.005 P =0.018, P =0.035), but there were no significant differences beween two groups in gender, whether there were B symptoms, whether LDH was elevated, whether there was extranodal involvement, cell origin, bone marrow infiltration, and whether rituximab was combined ( P =0.738, P =1, P =0.315, P =0.305, P =0.413, P =0.177, P =0.711, P =0.229). The efficacy could be evaluated in 36 cases, including CR 14 (38.9%), PR 17 (47.2%), PD 5 (13.9%), and ORR of 86.1% (31/36). There were no statistically significant differences in CR［(27.8%（5/18） vs 50.0%（9/18）; P >0.05］ and PR ［44.4%（8/18） vs 50.0%（9/18）; P >0.05］ of R±DHAX group and R-CHOP group, there was statistically significant difference in ORR［72.2%（13/18） vs 100.0%（18/18）; P =0.045］ between two groups. The 1-year OS of R±DHAX group and R-CHOP group was (38.9±11.5%)% and (94.4±7.4%)%, respectively, 2-year OS was (16.7±8.8)% and (72.2±10.6)%, respectively, and the differences between two groups were statistically significant ( P =0.001, P =0.002). The median survival time in the R±DHAX group was 11 months(95%CI :8.9-13.1), and the median survival time in the R-CHOP group was not reached, and there was a statistically significant difference between the groups (P < 0.001). For elderly DLBCL patients, R±DHAX may not be superior to R-CHOP in OS, and ECOG score, IPI score and age may affect the survival of elderly DLBCL patients. However, R±DHAX regimen is safe, tolerable and has a certain efficacy, which can be used as one of the clinical treatment options for elderly DLBCL.

Phase 3 trial of odronextamab plus lenalidomide versus rituximab plus lenalidomide in relapsed/refractory (R/R) follicular lymphoma (FL) and marginal zone lymphoma (MZL; OLYMPIA-5).

TPS7094 Background: FL and MZL are indolent B-cell non-Hodgkin lymphomas (B-NHLs) that are treated in a similar way in the R/R setting. Despite the efficacy of rituximab–lenalidomide (R2) in patients (pts) with R/R FL, and MZL to a lesser extent, a notable proportion fail to achieve an optimal, durable response. Odronextamab is an off-the-shelf, CD20×CD3 bispecific antibody. In the Phase (Ph) 1 ELM-1 study, odronextamab monotherapy showed antitumor activity and a generally manageable safety profile across R/R B-NHL subtypes, including FL and MZL (Bannerji, et al. Lancet Haematol 2022). In the Ph 2 ELM-2 study, odronextamab elicited an objective response rate of 80% and complete response (CR) rate of 73% in pts with heavily pretreated R/R FL (Villasboas, et al. ASH 2023). The rate of treatment-related adverse events leading to treatment discontinuation was 7.8%. These positive data support the evaluation of odronextamab in R/R FL and MZL in earlier lines of therapy. Combining odronextamab with lenalidomide has the potential to improve efficacy in the R/R setting compared with R2. Methods: OLYMPIA-5 (NCT06149286) is a Ph 3, open-label, randomized study of odronextamab plus lenalidomide versus R2 in pts with R/R FL and MZL. The study consists of Part 1 (safety run-in) followed by Part 2 (randomization). In Part 1, odronextamab and lenalidomide will be administered for 12×28-day cycles or until relapse, progressive disease, withdrawal of consent, or unacceptable toxicity. Odronextamab IV infusion will be administered in a step-up regimen during Cycle (C) 1 to mitigate the risk of cytokine release syndrome, followed by full dose starting from C1 Day 22. In Part 2, pts will be randomized 1:1 to receive 12 cycles of odronextamab plus lenalidomide, or R2 for the first 5 cycles followed by lenalidomide monotherapy for C6–12 per standard schedule (Leonard, et al. J Clin Oncol 2019). Key inclusion criteria: aged ≥18 years; histologically confirmed FL Grade 1–3a or MZL (nodal, splenic, or extra nodal) that is refractory or relapsed after ≥2 cycles of prior systemic therapy that included ≥1 anti-CD20 antibody; measurable disease; ECOG PS 0–2; and adequate organ function. Pts with central nervous system (CNS) lymphoma, history of or current relevant CNS pathology, histological evidence of transformation to high-grade or diffuse large B-cell lymphoma, and prior use of lenalidomide or any CD20×CD3 bispecific antibody within the past 6 months are excluded. The Part 2 primary endpoint is progression-free survival as assessed by independent central review. Key secondary endpoints are CR, best overall response, and overall survival. Minimal residual disease (by ctDNA) analysis is an exploratory endpoint. The trial is currently recruiting and is expected to enroll approximately 24–48 pts in Part 1 and 422 pts in Part 2 (352 R/R FL; 70 R/R MZL) at ~200 global sites. Clinical trial information: NCT06149286 .

Comparison of rituximab efficacy in treatment-naive and refractory inflammatory myopathies: experiences from a tertiary care centre.

To find out if Rituximab (RTX) is effective in "treatment naive" idiopathic inflammatory myopathies (IIM), and whether there could be differential treatment responses between the "treatment naive" and treatment "refractory" IIM. Data obtained from a prospectively maintained database comprising patients with IIM treated with rituximab. Patient details were obtained at baseline, 3-months, 6-months intervals, and subsequent follow up visits. Treatment response was categorised as improved, worsening, or stable based on manual muscle testing (MMT8) scores, patient global and physician global improvement (PtGA and PGA) for skin and joint symptoms improvement and spirometry at 6 months. The time to clinical improvement and remission were noted and survival analysis curves were constructed. 60 patients with IIM (including 18 with anti-SRP myopathy) were included, out of which 33 who received RTX were treatment naïve. The remaining 27 were started on rituximab for refractory myopathy. Mean age was 39 years (SD12.58) in "treatment-naive" group and 43 years (SD 12.12) in "refractory" group. At 6 months of follow up, 48/55 (87%) patients showed response, 31/31 (100%) in "treatment-naive" and 17/24 (70%) in "refractory" cases, p 0.006*. In refractory group, 7 (29%) had stable disease. The mean changes in MMT8 were significantly more in the "treatment-naive" treatment group (13.41(SD 7.31) compared with "refractory" IIM 8.33 (SD 7.92) (p= 0.017*). Majority of patients were able to reduce dose below 5 mg/day before 6 months. No major adverse events were reported over the median follow-up of 24 (IQR 36) months. Rituximab is effective and safe across the spectrum of IIM. Early use in disease is associated with better outcomes.

Rituximab is a safe and effective alternative treatment for patients with autoimmune hepatitis: Results from the ColHai registry.

Small series suggest that rituximab could be effective as treatment for autoimmune hepatitis (AIH), although data are scarce. We aimed to evaluate the efficacy and safety of rituximab in different cohorts of patients with AIH. Multicentre retrospective analysis of the 35 patients with AIH and its variant forms treated with rituximab and included in the ColHai registry between 2015 and 2023. Most patients were female (83%), 10 (29%) had cirrhosis and four (11.4%) variant forms of AIH. Indication for rituximab were as follows: 14(40%) refractory AIH, 19(54%) concomitant autoimmune or haematological disorder, 2(6%) intolerance to prior treatments. In three (9%) subjects with a concomitant disorder, rituximab was the first therapy for AIH. Overall, 31 (89%) patients achieved or maintained complete biochemical response (CBR), including the three in first-line therapy. No difference in CBR was observed according to rituximab indication (refractory AIH 86% vs. concomitant disorders 90%, p = .824) or cirrhosis (80% vs. 92%, p = .319). Rituximab was associated with a significant reduction in corticosteroids (median dose: prior 20 vs. post 5 mg, p < .001) and the discontinuation of ≥1 immunosuppressant in 47% of patients. Flare-free rate at 1st, 2nd and 3rd year was 86%, 73% and 62% respectively. Flares were not associated with the development of liver failure and were successfully managed with repeated doses of rituximab and/or increased corticosteroids. Three (9%) patients experienced infusion-related adverse events (1 anaphylaxis and 2 flu-like symptoms) and five (14%) infections. Rituximab is safe and effective in patients with refractory AIH and those treated due to concomitant autoimmune or haematological disorders.

Efficacy of rituximab in treating steroid-resistant Graves’ orbitopathy in active moderate-to-severe and sight-threatening forms: A retrospective observation from China

Background and objectivesThe efficacy of rituximab (RTX) in treating steroid-resistant Graves’ orbitopathy (GO) has been limitedly studied in Asians. Moreover, RTX has been considered even less for patients with steroid-resistant dysthyroid optic neuropathy (DON) who failed to undergo orbital decompression surgery for physical or financial reasons, or who responded poorly to the procedure. This study aimed to investigate the efficacy of RTX in treating steroid-resistant active moderate-to-severe and sight-threatening GO in a Chinese population. MethodsData from 28 patients with steroid-resistant GO prescribed a single dose of 500 mg RTX were retrospectively retrieved. Treatment responses and contributing factors were analyzed. ResultsThe median follow-up time was 22 (8–34) weeks. 23 (82.1 %) patients had a positive objective outcome recommended by the European Group on Graves’ Orbitopathy (EUGOGO), while 25 (92.6 %) had a decrease in 7-item clinical activity score (CAS) by at least 2. Diplopia, visual dysfunction, and MRI-detected T2 relaxation time of the involved extraocular muscles improved significantly at the last follow-up compared to baseline (81.0 % vs. 47.6 %, 38.9 % vs. 16.7 %, and 87.8 (8.64) vs. 75.8 (10.9) ms, respectively; all p values < 0.05). No significant improvement was seen in terms of proptosis and eye muscle duction. Notably, a higher baseline IgG4 to IgG ratio was a predictor for RTX-induced positive EUGOGO outcomes. After RTX treatment, all 8 patients with DON demonstrated inactivation, and 4 improved in visual acuity by ≥ 1 line. No patient with DON experienced obvious deterioration. ConclusionA single dose of 500 mg RTX seemed to be an effective and tolerable treatment for steroid-resistant GO. However, larger-scale studies with a control group are required for a more solid conclusion. The role of RTX in steroid-resistant DON management where surgery is unavailable or ineffective should be further explored.

Acalabrutinib plus venetoclax and rituximab in treatment-naive mantle cell lymphoma: 2-year safety and efficacy analysis

AbstractThis phase 1b study evaluated safety and efficacy of acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive mantle cell lymphoma (TN MCL). Patients received acalabrutinib from cycle 1 until progressive disease (PD) or undue toxicity, rituximab for 6 cycles with maintenance every other cycle through cycle 24 or until PD, and venetoclax, beginning at cycle 2, for 24 cycles. Twenty-one patients were enrolled; 95.2% completed induction (6 AVR cycles) and 47.6% continued acalabrutinib maintenance. Thirteen (61.9%) patients had grade 3-4 adverse events (AEs), most commonly neutropenia (33.3%). Seven (33.3%) patients had COVID-19 infection (6 [28.6%] serious AEs and 5 [23.8%] deaths, all among unvaccinated patients). There was no grade ≥3 atrial fibrillation, ventricular tachyarrhythmias, major hemorrhages, or tumor lysis syndrome. Overall response rate (ORR) was 100% (95% CI, 83.9-100.0) with 71.4% complete response. With median follow-up of 27.8 months, median progression-free survival (PFS) and overall survival (OS) were not reached. PFS rates at 1 and 2 years were 90.5% (95% CI, 67.0-97.5) and 63.2% (95% CI, 34.7-82.0), respectively; both were 95% after censoring COVID-19 deaths. OS rates at 1 and 2 years were 95.2% (95% CI, 70.7-99.3) and 75.2% (95% CI, 50.3-88.9), respectively; both were 100% after censoring COVID-19 deaths. Overall, 87.5% of patients with available minimal residual disease (MRD) data achieved MRD negativity (10–6; next-generation sequencing) during treatment. AVR represents a chemotherapy-free regimen for TN MCL and resulted in high ORR and high rates of MRD negativity. The trial was registered at www.ClinicalTrials.gov as #NCT02717624.

Interstitial Lung Disease Associated with Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by a tripod combining vasculopathy, fibrosis, and immune-mediated inflammatory processes. The prevalence of interstitial lung disease (ILD) in SSc varies according to the methods used to detect it, ranging from 25 to 95%. The fibrotic and vascular pulmonary manifestations of SSc, particularly ILD, are the main causes of morbidity and mortality, contributing to 35% of deaths. Although early trials were conducted with cyclophosphamide, more recent randomized controlled trials have been performed to assess the efficacy and tolerability of several medications, mostly mycophenolate, rituximab, tocilizumab, and nintedanib. Although many uncertainties remain, expert consensus is emerging to optimize the therapeutic management and to provide clinicians with evidence-based clinical practice guidelines for patients with SSc-ILD. This article provides an overview, in the light of the latest advances, of the available evidence for the diagnosis and management of SSc-ILD.

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.