A patient treated with ofatumumab for myasthenia gravis in conjunction with systemic lupus erythematosus and thyroid carcinoma.

Myasthenia gravis (MG) is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK) antibodies in the postsynaptic membrane at the neuromuscular junction. Anti-CD20 monoclonal antibodies, such as ofatumumab demonstrated promising disease control in MG patients. We presented the rare case of a 34-year-old female with acetylcholine receptor-positive myasthenia gravis (AChR-MG), concomitant with systemic lupus erythematosus (SLE) and metastatic thyroid carcinoma, who was treated with ofatumumab and exhibited improvements during follow-up.

Efficacy of Combination of Antiviral Therapy With Neutralizing Monoclonal Antibodies for Recurrent Persistent SARS-CoV-2 Pneumonia in Patients With Lymphoma.

Despite the potential of neutralizing antibodies in the management of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), clinical research on its efficacy in Chinese patients remains limited. This study is aimed at investigating the therapeutic effect of combination of antiviral therapy with neutralizing monoclonal antibodies for recurrent persistent SARS-CoV-2 pneumonia in patients with lymphoma complicated by B cell depletion. A prospective study was conducted on Chinese patients who were treated with antiviral nirmatrelvir/ritonavir therapy and the neutralizing antibody tixagevimab-cilgavimab (tix-cil). The primary outcome was the rate of recurrent SARS-CoV-2 infection. Five patients with lymphoma experienced recurrent SARS-CoV-2 pneumonia and received tix-cil treatment. All patients had a history of CD20 monoclonal antibody use within the year preceding SARS-CoV-2 infection, and two patients also had a history of Bruton's tyrosine kinase (BTK) inhibitor use. These patients had notably low lymphocyte counts and exhibited near depletion of B cells. All five patients tested negative for serum SARS-CoV-2 IgG and IgM antibodies. None of the patients developed reinfection with SARS-CoV-2 pneumonia after antiviral and tix-cil treatment during the 6-month follow-up period. In conclusion, the administration of antiviral and SARS-CoV-2-neutralizing antibodies showed encouraging therapeutic efficacy against SARS-CoV-2 pneumonia in patients with lymphoma complicated by B cell depletion, along with the potential preventive effect of neutralizing antibodies for up to 6 months.

Anti-IL12p40 autoantibodies in a teenage girl with multiple recurrent abscesses.

More frequent among adults, phenocopies may be caused by somatic mutations or anti-cytokine autoantibodies, mimicking the phenotypes of primary immunodeficiencies. A fourteen-year-old girl was referred for a two-year history of weight loss and multiple recurrent abscesses, complicated recurrent pneumonia, pyelonephritis, osteomyelitis, and septic shock, without fever. She had started with nausea, hyporexia, and weight loss, then with abscesses in her hands, knee, ankle, and spleen. She also developed a rib fracture and left thoracic herpes zoster. The patient was cachectic, with normal vital signs, bilateral crackles on chest auscultation, tumefaction of the knee joint, and poorly healed wounds in hands and chest, oozing a yellowish fluid. Chest computed tomography revealed multiple bilateral bronchiectases. Laboratory workup reported chronic anemia, leukocytosis, neutrophilia, mild lymphopenia, thrombocytosis, pan-hypergammaglobulinemia, and elevated acute serum reactants. Lymphocyte subsets were low but present. Mycobacterium tuberculosis was detected via polymerase chain reaction in a bone biopsy specimen from ankle osteomyelitis. Whole-exome sequencing failed to identify a monogenic defect. Interleukin-12 was found markedly elevated in the serum of the patient. Phosphorylation of STAT4, induced by increasing doses of IL-12, was neutralized by patient serum, confirming the presence of anti-IL12 autoantibodies. IL-12 and IL-23 are crucial cytokines in the defense against intracellular microorganisms, the induction of interferon-gamma production by lymphocytes, and other inflammatory functions. Patients who develop neutralizing serum autoantibodies against IL12 manifest late in life with weight loss, multiple recurrent abscesses, poor wound healing, and fistulae. Treatment with anti-CD20 monoclonal antibodies was effective.

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

Background: CD20 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. Methods: A 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. Results: All 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. Conclusion: This 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.

Identification and characterization of circulating and adipose tissue infiltrated CD20+T cells from subjects with obesity that undergo bariatric surgery.

T cells play critical roles in adipose tissue (AT) inflammation. The role of CD20+T cell in AT dysfunction and their contributing to insulin resistance (IR) and type 2 diabetes progression, is not known. The aim was to characterize CD20+T cells in omental (OAT), subcutaneous (SAT) and peripheral blood (PB) from subjects with obesity (OB, n = 42), by flow cytometry. Eight subjects were evaluated before (T1) and 12 months post (T2) bariatric/metabolic surgery (BMS). PB from subjects without obesity (nOB, n = 12) was also collected. Higher percentage of CD20+T cells was observed in OAT, compared to PB or SAT, in OB-T1. CD20 expression by PB CD4+T cells was inversely correlated with adiposity markers, while follicular-like CD20+T cells were positively correlated with impaired glucose tolerance (increased HbA1c). Notably, among OB-T1, IR establishment was marked by a lower percentage and absolute number of PB CD20+T cells, compared nOB. Obesity was associated with higher percentage of activated CD20+T cells; however, OAT-infiltrated CD20+T cells from OB-T1 with diabetes displayed the lowest activation. CD20+T cells infiltrating OAT from OB-T1 displayed a phenotype towards IFN-γ-producing Th1 and Tc1 cells. After BMS, the percentage of PB CD4+CD20+T cells increased, with reduced Th1 and increased Th17 phenotype. Whereas in OAT the percentage of CD20+T cells with Th1/17 and Tc1/17 phenotypes increased. Interestingly, OAT from OB pre/post BMS maintained higher frequency of effector memory CD20+T cells. In conclusion, CD20+T cells may play a prominent role in obesity-related AT inflammation.

The evaluation of risk factors for prolonged viral shedding during anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antivirals in COVID-19 patients with B-cell lymphoma treated by anti-CD20 antibody.

BACKGROUND: The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection. METHODS: This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression. RESULTS: Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10-20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19-38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding. CONCLUSIONS: Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.

Nodal T follicular helper cell lymphoma with aberrant CD20 expression and monoclonal TCR, IG rearrangements secondary to Classical Hodgkin Lymphoma: a case report.

Classical Hodgkin Lymphoma (CHL) is a rare malignant neoplasm of the lymphatic system. While CHL typically responds well to conventional treatments, some cases may experience relapse to other subtypes, with the development of secondary peripheral T-cell lymphoma (PTCL) being relatively uncommon. Herein, we report a rare case of nodal T follicular helper cell lymphomas,nos (nTFHL-NOS) secondary to CHL, accompanied by aberrant CD20 expression and clonal rearrangements of T-cell receptor (TCR) and immunoglobulin (IG). A 74-year-old male, was diagnosed with CHL, leaning toward the mixed cell type, 6 years ago. He received six cycles of the Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) regimen, achieving complete clinical remission. The patient was admitted to our hospital due to the appearance of multiple skin nodules 66 months later. Histopathological analysis revealed nTFHL-NOS, with aberrant CD20 expression and clonal rearrangements of TCR and IG. The patient underwent two cycles of chemotherapy with brentuximab vedotin and the Gemcitabine-Oxaliplatin (G-mox) regimen, resulting in a reduction of the skin lesions to 2 cm × 1 cm. We discuss this rare case and review related literature.

A Comprehensive Study on Aberrant CD20-Positive Mycosis Fungoides: Clinical and Prognostic Insights.

BACKGROUND: As the majority of T-cell lymphomas lack CD20 expression, cases of mycosis fungoides (MF) exhibiting aberrant CD20 expression are exceedingly uncommon. OBJECTIVES: We aim to comprehensively evaluate the clinical, histopathological, and prognostic features of 7 patients diagnosed with CD20-positive MF. METHODS: This retrospective study examines seven cases of MF with aberrant CD20 expression. The study provides details of demographics, clinical features, histopathology and treatment outcomes. Key time points include initial diagnosis of MF, detection of CD20 expression and follow-up, with a mean follow-up of 46 months. RESULTS: Aberrant CD20-positive MF was diagnosed at an average age of 58.6 years, approximately 5.6 years after first MF diagnosis. Following CD20 detection, patients presented with advanced disease stages, requiring treatments such as chemotherapy, brentuximab vedotin, and allogeneic hematopoietic stem cell transplantation. Four patients died from lymphoma, with an average survival time of 52 months. CONCLUSIONS: Aberrant CD20 expression in MF is rare but indicates a progressive course associated with poor prognosis. This often requires systemic chemotherapy and, in certain instances, allogeneic hematopoietic stem cell transplantation. This study provides important insights into the clinical attributes, disease progression, and treatment options for MF patients with aberrant CD20 expression. Further research is necessary to validate the effectiveness of emerging therapies and enhance our understanding of the underlying mechanisms and prognostic determinants specific to this unique MF subgroup.

Evaluation of anti-vector immune responses to adenovirus-mediated lung gene therapy and modulation by αCD20.

Although the last decade has seen tremendous progress in drugs that treat cystic fibrosis (CF) due to mutations that lead to protein misfolding, there are approximately 8%-10% of subjects with mutations that result in no significant CFTR protein expression demonstrating the need for gene editing or gene replacement with inhaled mRNA or vector-based approaches. A limitation for vector-based approaches is the formation of neutralizing humoral responses. Given that αCD20 has been used to manage post-transplant lymphoproliferative disease in CF subjects with lung transplants, we studied the ability of αCD20 to module both T and B cell responses in the lung to one of the most immunogenic vectors, E1-deleted adenovirus serotype 5. We found that αCD20 significantly blocked luminal antibody responses and efficiently permitted re-dosing. αCD20 had more limited impact on the T cell compartment, but reduced tissue resident memory T cell responses in bronchoalveolar lavage fluid. Taken together, these pre-clinical studies suggest that αCD20 could be re-purposed for lung gene therapy protocols to permit re-dosing.

Optimizing Ex Vivo CAR-T Cell-Mediated Cytotoxicity Assay through Multimodality Imaging.

CAR-T cell-based therapies have demonstrated remarkable efficacy in treating malignant cancers, especially liquid tumors, and are increasingly being evaluated in clinical trials for solid tumors. With the FDA's initiative to advance alternative methods for drug discovery and development, full human ex vivo assays are increasingly essential for precision CAR-T development. However, prevailing ex vivo CAR-T cell-mediated cytotoxicity assays are limited by their use of radioactive materials, lack of real-time measurement, low throughput, and inability to automate, among others. To address these limitations, we optimized the assay using multimodality imaging methods, including bioluminescence, impedance tracking, phase contrast, and fluorescence, to track CAR-T cells co-cultured with CD19, CD20, and HER2 luciferase reporter cancer cells in real-time. Additionally, we varied the ratio of CAR-T cells to cancer cells to determine optimal cytotoxicity readouts. Our findings demonstrated that the CAR-T cell group effectively attacked cancer cells, and the optimized assay provided superior temporal and spatial precision measurements of ex vivo CAR-T killing of cancer cells, confirming the reliability, consistency, and high throughput of the optimized assay.

Peptide-based CE-SELEX enables convenient isolation of aptamers specifically recognizing CD20-expressing cells.

The CD20 antigen is a key target for several diseases including lymphoma and autoimmune diseases. For over 20 years, several monoclonal antibodies were developed to treat CD20-related disorders. As many therapeutic proteins, their clinical use is however limited due to their nature with a costly biotechnological procedure and side effects such as the production of anti-drug neutralizing antibodies. Nucleic acid aptamers have some advantages over mAbs and are currently investigated for clinical use. We herein report the selection of DNA aptamer by using a peptide-based CE-SELEX (Capillary Electrophoresis-Systematic Evolution of Ligands by Exponential Enrichment) method. It was demonstrated that these aptamers bind specifically a CD20-expressing human cell line, with Kd estimated from isothermal titration calorimetry experiments in the micromolar range. This study demonstrates that the CE-SELEX is suitable as alternative method to the conventional Cell-SELEX to discover new cell-targeting compounds.

Salvage CD20-SD-CART therapy in aggressive B-cell lymphoma after CD19 CART treatment failure.

Background and aims: Patients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure. Methods: This retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab). Results: A total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p<0.0001) compared to the non-CART group. The complete response rate in the CD20-SD-CART group (15/54, 27.8%) was also significantly higher than the non-CART group (3/38, 7.9%, p=0.03). Multivariate analysis further confirmed that CD20CART treatment was independently associated with improved overall survival (HR, 0.28; 95% CI, 0.16-0.51; p<0.0001) and progression-free survival (HR, 0.46; 95% CI, 0.27-0.8; p=0.005). Conclusion: CD20-SD-CART could serve as an effective therapeutic option for patients with relapsed or refractory aggressive B-cell lymphoma after CD19CART treatment failure.

Efficacy and safety of MIL62, a novel glycoengineered type â ¡ anti-CD20 monoclonal antibody, combined with lenalidomide in patients with relapsed/refractory follicular lymphoma or marginal zone lymphoma: a multicentre, single-arm, phase 1b/2 trial.

Background: MIL62, a novel glycoengineered type Ⅱ anti-CD20 monoclonal antibody, with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively. Methods: This multicentre, single-arm, phase 1b/2 trial aimed to explore the efficacy, pharmacokinetics, and safety of MIL62 combined with lenalidomide in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Eligible patients included those who had histopathologically confirmed CD20 positive FL (grade 1-3a) or MZL and failed to be treated with rituximab. Patients received intravenously infused MIL62 1000 mg (cycle 1: day 1, 15; cycles 2-8: day 1, cycles 10 and 12: day 1) combined with oral lenalidomide (once a day, days 2-22, the initial dose was 10 mg, and the maximum dose was 20 mg) for 12 cycles, 28 days as a cycle. The primary endpoint was objective response rate (ORR) assessed by investigator per Lugano 2014 criteria every 3 cycles. This study was registered in ClinicalTrials.gov (NCT04110301). Findings: Between November 22, 2019 and December 22, 2020, 54 patients were enrolled from 11 hospitals in China and received study treatment. Fifty patients were included in the efficacy analysis set, and 43 patients (86%, 95% CI: 73, 94) achieved objective response, meeting the pre-specified primary endpoint. Disease control rate was 96% (48/50, 95% CI: 86, 100), proportion of patients with duration of response (DoR) > 6 months was 77% (33/43). The median follow-up for survival was 12.3 months (IQR 12.0-12.6). The 1-year progression-free survival rate was 72% (95% CI: 57, 83), 9-month DoR rate was 74% (95% CI: 58, 85), and 1-year overall survival rate was 98% (95% CI: 85, 100). Most common TRAEs were neutropenia (93%, 50/54), leukopenia (85% 46/54), thrombocytopenia (61% 33/54), lymphopenia (32% 17/54), and alanine aminotransferase increased (20% 11/54). Interpretation: MIL62 combined with lenalidomide showed promising efficacy in patients with R/R FL and MZL. A multicentre, randomized, open-label, phase Ⅲ trial of MIL62 combined with lenalidomide versus lenalidomide in anti-CD20 monoclonal antibody refractory FL patients is ongoing (NCT04834024). Funding: Beijing Mabworks Biotech Co. Ltd, Beijing China and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Intratumoral T-cell composition predicts epcoritamab-based treatment efficacy in B-cell non-Hodgkin lymphomas.

Leveraging endogenous tumor-resident T-cells for immunotherapy using bispecific antibodies (BsAb) targeting CD20 and CD3 has emerged as a promising therapeutic strategy for patients with B-cell non-Hodgkin lymphomas. However, features associated with treatment response or resistance are unknown. To this end, we analyzed data from patients treated with epcoritamab-containing regimens in the EPCORE NHL-2 trial (NCT04663347). We observed downregulation of CD20 expression on B-cells following treatment initiation both in progressing patients and in patients achieving durable complete responses (CR), suggesting that CD20 downregulation does not universally predict resistance to BsAb-based therapy. Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.

A phase 2 study of spartalizumab (PDR001) among patients with recurrent or metastatic esophageal squamous cell carcinoma (KCSG HN18-17, K-MASTER project 12).

Spartalizumab (PDR001) is a humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We conducted a single-arm, phase 2 trial to investigate the efficacy and safety of spartalizumab in patients with refractory esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC who experienced disease progression after platinum-based chemotherapy received 300 mg of intravenous spartalizumab every three weeks until disease progression or occurrence of unacceptable toxicity. The primary endpoint was centrally assessed objective response according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were closely monitored throughout the study. From March 2020 through April 2021, 44 patients with ESCC were enrolled. Of the 44 patients, the objective response rate was 20.5% (95% confidence interval: 8.5-32.4). With a median follow-up of 10.9 months, median progression-free survival and overall survival were 3.2 months and 11.2 months, respectively. In addition, the median duration of response was 24.7 months. The most common grade 3 or 4 adverse event was grade 3 dysphagia (eight [18%] patients). Biomarker analyses explored programmed cell death ligand 1 and CD20 as potential predictive markers for PD-1 blockade. Spartalizumab showed promising activity with a manageable safety profile, indicating its potential as a new treatment option for patients with refractory ESCC. Trial registration: The trial was registered at ClinicalTrials.gov under the identifier NCT03785496.

CDR grafting and site-directed mutagenesis approach for the generation and affinity maturation of Anti-CD20 nanobody.

BACKGROUND: Recently, new and advanced techniques have been adopted to design and produce nanobodies, which are used in diagnostic and immunotherapy treatments. Traditionally, nanobodies are prepared from camelid immune libraries that require animal treatments. However, such approaches require large library sizes and complicated selection procedures. The current study has employed CDR grafting and site-directed mutagenesis techniques to create genetically engineered nanobodies against the tumor marker CD20 (anti-CD20 nanobodies) used in leukemia treatment. METHODS AND RESULTS: In this study, we utilized the swapping method to graft CDRs from the VH Rituximab antibody to VHH CDRs. We aimed to enhance the binding affinity of the nanobodies by substituting the amino acids (Y101R-Y102R-Y107R) in the VHH-CDR3. To assess the binding capacity of the mutated nanobodies, we conducted an ELISA test. Moreover, through flow cytometry analysis, we compared the fluorescence intensity of the grafted CD20 and mutant nanobodies with that of the commercially available human anti-CD20 in Raji cells. The results showed a significant difference in the fluorescence intensity of the grafted nanobodies and mutant nanobodies when compared to the commercially available human anti-CD20. CONCLUSION: The approach we followed in this study makes it possible to create multiple anti-CD20 nanobodies with varying affinities without the need for extensive selection efforts. Additionally, our research has demonstrated that computational tools are highly reliable in designing functional nanobodies.

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

Objectives: 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). Materials and methods: 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. Results: 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. Conclusion: 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.

Bronchiectasis, lymphadenopathies related to BAFF overexpression and lymphoplasmacytic cystitis as adverse events associated with prolonged use of rituximab in systemic autoimmune rheumatic diseases.

BACKGROUND: The long-term use of rituximab (RTX) has been gaining ground in the treatment of systemic autoimmune diseases. The adverse events (AEs) associated with its use different to infections are being reported. METHODS: A cohort of patients with SAIDs treated at a high-complexity center in Cali (southwestern Colombia) with follow-up from January 2008 to December 2022 were examined to search for potential AEs associated with prolonged use of RTX. RESULTS: From 178 patients with long-term use of RTX 3 (1.68%) had lymphadenopathies with lymphoid follicular hyperplasia related to BAFF overexpression, 4 (2.24%) with bronchiectasis, and 4 (2.24%) with lymphoplasmacytic cystitis. CONCLUSION: Bronchiectasis, lymphoid follicular hyperplasia related to BAFF overexpression, and lymphoplasmacytic cystitis may be life-threatening long-term AEs in patients with prolonged use of RTX.

CD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies.

Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients. Therefore, novel approaches to treat aggressive lymphomas are being intensively investigated. Several RTX-resistant (RR) cell lines have been established as surrogate models to study resistance to R-CHOP. Our study reveals that RR cells are characterized by a major downregulation of CD37, a molecule currently explored as a target for immunotherapy. Using CD20 knockout (KO) cell lines, we demonstrate that CD20 and CD37 form a complex, and hypothesize that the presence of CD20 stabilizes CD37 in the cell membrane. Consequently, we observe a diminished cytotoxicity of anti-CD37 monoclonal antibody (mAb) in complement-dependent cytotoxicity in both RR and CD20 KO cells that can be partially restored upon lysosome inhibition. On the other hand, the internalization rate of anti-CD37 mAb in CD20 KO cells is increased when compared to controls, suggesting unhampered efficacy of antibody drug conjugates (ADCs). Importantly, even a major downregulation in CD37 levels does not hamper the efficacy of CD37-directed chimeric antigen receptor (CAR) T cells. In summary, we present here a novel mechanism of CD37 regulation with further implications for the use of anti-CD37 immunotherapies.