Rituximab Injection Research Articles

Management of primary choroidal lymphoma presenting as extensive serous retinal detachment and salmon patch of bulbar conjunctiva: a case report

BackgroundWe describe the outcome of ultra-low-dose radiotherapy plus intravitreal methotrexate and rituximab injections for a patient with primary choroidal lymphoma who presented with nodular conjunctival salmon patches and extensive serous retinal detachment.Case presentationA 34-year-old Iranian man presented with a nodular patch of bulbar conjunctiva in the right eye, and 1+ vitritis. A nearly complete shallow serous retinal detachment, retinal folds, and multifocal yellow choroidal infiltrates were seen during a fundus examination of the right eye. Enhanced depth imaging optical coherence tomography revealed macular retinal folds and an uneven, undulating, “seasick” appearance of the choroidal surface with choriocapillaris compression, intraretinal and subretinal fluid, and clusters of optically dense material at the outer retinal level. An incisional biopsy of the conjunctival lesion confirmed the diagnosis of primary choroidal lymphoma with epibulbar involvement. The patient was treated with ultra-low-dose “boom-boom” radiation (4 Gy delivered in two fractions over two consecutive days) as well as intravitreal methotrexate and rituximab injections. After a year, the lesions had completely disappeared, with no adverse effects or recurrence.ConclusionUltra-low-dose (boom-boom) radiotherapy combined with intravitreal chemotherapy and/or immunotherapy may be an effective treatment for primary choroidal lymphoma with anterior epibulbar extension and diffuse subretinal fluid with favorable response and minimal side effects.

Assessing quality of life in patients with autoimmune bullous diseases using the Persian version of Treatment of Autoimmune Bullous Disease Quality of Life questionnaire finds similar effects in women as men.

Background:In autoimmune bullous diseases (AIBDs), autoantibodies loosen molecular adhesions in the skin and/or mucosa and lead to blisters and erosions. Immunosuppressive drugs reduce mortality of the AIBD; therefore, patients will have to live longer with comorbidities.Objective:This study aims to determine the quality of life of AIBD patients undergoing systemic treatment while investigating the survey’s relationship with various factors.Methods:In this 2-step cross-sectional study, we initially included 53 consecutive pemphigus patients to investigate reliability and validity of the Persian version of Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaire. Then, we conducted the study on 119 AIBD patients, currently under treatment at an AIBD clinic in Iran.Results:The mean TABQOL score for our patients was 13.87 ± 7.51. The highest TABQOL was for epidermolysis bullosa acquisita (24 ± 8.485) followed by pemphigus foliaceus (20.5 ± 14.181) and the lowest for pemphigus vulgaris (13.24 ± 6.54). There was no significant difference between patients’ TABQOL scores and their gender, history of rituximab injection, and disease severity scores. We only found a positive correlation between TABQOL and prednisolone dose.Conclusion:Treatments of AIBD considerably impact the quality of life of patients and an impairment in quality of life is correlated to higher doses of prednisolone.

Effect of rituximab on reducing the panel-reactive antibody in dialysis patients of transplant candidate

Introduction: Based on the evidence, rituximab may be an effective treatment for kidney transplantation for reducing panel-reactive antibody. Objectives: This study was conducted to investigate the effect of rituximab on reducing the panel in transplant dialysis patients. Patients and Methods: This is an interventional study that was conducted on 20 dialysis patients who were candidates for kidney transplantation. Patients first had a panel-reactive antibody test and patients with a panel-reactive antibody above the age of 30 were included in the study. First, rituximab was administered at a dose of one gram and then after two weeks, another dose of one gram was administered. Panel-reactive antibody was measured baseline, one and six months later. Results: One and six months after stopping the drug, we found a significant decrease in the mean amount of reactive antibodies. Additionally, six months after stopping the drug, a significant decrease in the level of patients’ reactive antibodies in comparison to one month before taking the drug was detected (P<0.05). Conclusion: The findings showed that treatment with rituximab is useful for reducing panel-reactive antibody in kidney transplant patients. However, more studies are needed to optimize rituximab injection protocols.

Rituximab Immunomonitoring Predicts Remission in Membranous Nephropathy.

Primary membranous nephropathy (pMN) is an autoimmune kidney disease and a common cause of nephrotic syndrome in adults. Rituximab is becoming a first line therapy for patients with persistent nephrotic syndrome with proven safety and efficacy, achieving remission in 60%–80% of cases. For the remaining 20%–40% of patients there is an urgent need to identify early biomarkers of resistance to rituximab to adapt therapeutic management. In nephrotic patients, rituximab is found in the blood more transiently than in other autoimmune diseases without proteinuria, due to rituximab wasting in the urine. However, rituximab immunomonitoring is not routinely performed. We evaluated the predictive value of serum rituximab levels in patients with pMN three months after rituximab injection (month-3) on clinical remission rates six months (month-6) and 12 months (month-12) after injection and investigated predictive factors for serum rituximab levels at month-3. Sixty-eight patients treated with rituximab between July 2015 and January 2020 from two French nephrology centers were included. We identified residual rituximab levels at month-3 as a novel early predictor of remission at month-6 (p <0.0001) and month-12 (p = 0.001). Reduced likelihood of remission in patients with undetectable rituximab at month-3 was associated with lower serum albumin and higher anti-PLA2R1 titers at baseline and with lower serum albumin, higher proteinuria, higher CD19+ counts and higher anti-PLA2R1 titers during follow-up. In multivariate analysis, high baseline proteinuria and undetectable rituximab levels at month-3 were independent risk factors for treatment failure at month-6 and high baseline weight and undetectable rituximab levels at month-3 were independent risk factors for treatment failure at month-12. We identified serum albumin at baseline as a predictive factor for serum rituximab levels at month-3. Patients with serum albumin below 22.5 g/L at baseline had an 8.66-fold higher risk of having undetectable rituximab levels at month-3. Therefore, rituximab immunomonitoring in pMN patients treated with rituximab would allow the detection of patients at risk of treatment failure as early as month-3. Studies are needed to assess whether patients with low residual rituximab levels at month-3 may benefit from an early additional course of rituximab.

Do JAK inhibitors affect immune response to COVID-19 vaccination? Data from the MAJIK-SFR Registry.

Do JAK inhibitors affect immune response to COVID-19 vaccination? Data from the MAJIK-SFR Registry.

Latent Adrenal Insufficiency: From Concept to Diagnosis.

Primary adrenal insufficiency (PAI) is a rare disease and potentially fatal if unrecognized. It is characterized by destruction of the adrenal cortex, most frequently of autoimmune origin, resulting in glucocorticoid, mineralocorticoid, and adrenal androgen deficiencies. Initial signs and symptoms can be nonspecific, contributing to late diagnosis. Loss of zona glomerulosa function may precede zona fasciculata and reticularis deficiencies. Patients present with hallmark manifestations including fatigue, weight loss, abdominal pain, melanoderma, hypotension, salt craving, hyponatremia, hyperkalemia, or acute adrenal crisis. Diagnosis is established by unequivocally low morning serum cortisol/aldosterone and elevated ACTH and renin concentrations. A standard dose (250 µg) Cosyntropin stimulation test may be needed to confirm adrenal insufficiency (AI) in partial deficiencies. Glucocorticoid and mineralocorticoid substitution is the hallmark of treatment, alongside patient education regarding dose adjustments in periods of stress and prevention of acute adrenal crisis. Recent studies identified partial residual adrenocortical function in patients with AI and rare cases have recuperated normal hormonal function. Modulating therapies using rituximab or ACTH injections are in early stages of investigation hoping it could maintain glucocorticoid residual function and delay complete destruction of adrenal cortex.

A clinical case of using therapeutic plasma exchange for the treatment of recurrent focal segmental glomerulosclerosis in a child after kidney transplantation

Background. Focal segmental glomerulosclerosis (FSGS) of the graft in kidney recipients is a rare and difficultto-diagnose post-kidney transplant complication, which can lead to graft loss and death of the recipient. A unified protocol is required for the treatment of this disease.Materials and methods. A 15-year-old female patient C. diagnosed with stage 5 chronic kidney disease as a result of steroid-resistant nephrotic syndrome with hematuria underwent a living related-donor kidney transplantation. On the third day after the operation, laboratory and imaging data showed kidney graft dysfunction. Patient examinations established the cause of the graft dysfunction – idiopathic nephrotic syndrome in FSGS.Results. For the treatment of recurrent FSGS, the patient had her immunosuppressive therapy converted from tacrolimus to cyclosporin A, and received two 500 mg rituximab injections. Ten sessions of therapeutic plasma exchange (Plasauto Sigma) were performed to remove antibodies to podocytes. During the therapy, diuresis was restored, creatinine and urea levels decreased. Six months after the kidney transplant, graft function was fully restored. Conclusion. The absence of recurrent FSGS within six months during a single course of therapeutic plasma exchange with its subsequent cancellation after restoration of graft function allows to recommend the developed method for the treatment of FSGS in pediatric patients after kidney transplantation.

Home Administration of Subcutaneous Rituximab Is Safe and Associated with Significant Cost Saving: A Single Center Experience

IntroductionRituximab is as a cornerstone of treatment of B-cell malignancies, given as monotherapy (including maintenance after induction) or in combination with chemotherapy. While developed as IV infusion, subcutaneous formulation is now available. It has been demonstrated that, compared to IV infusion, subcutaneous injection is quicker (5 minutes injection), easier to manage and non-inferior with respect to efficacy, in follicular lymphoma, chronic lymphocytic leukemia, and diffuse large B-cell lymphoma. Home administration of chemotherapies for patients treated for hematological malignancies is widely used, as it has demonstrated safety, cost saving and improvement of quality of life. However, few datas have been reported for monoclonal antibodies.ObjectivesThe aim of our study was to describe our experience of home administration of SC rituximab to evaluate feasibility, safety and back to in-hospital administration. We also compared costs to in-hospital administration.MethodsWe included consecutive patients treated with at least one SC rituximab injection at home, from January 2016 to July 2017. All patients received approved dosage, ie.1400 mg. Patients received before injection paracetamol, prednisone and dexchlorpheniramine. Patients were eligible if 1°) they have previously received at least one IV infusion and one SC injection in ambulatory unit of our institution; 2°) they did not experienced adverse reaction to both administrations; 3°) they did not present comorbidity that require medical evaluation before each injection; 4°) their home was considered adequate for safe administration; 5°) they consented to home administration.ResultsWe included 39 patients; median age was 71y (range: 40 to 88), 25 females and 14 males. Median CIRS was 3 (range: 0 to 10). Majority of patients had hematological malignancies (follicular lymphoma: n=25, mantle cell lymphomas: n=7, marginal zone lymphoma: n=3, hairy cell leukemia: n=1) and 3 had autoimmune hemolytic anemias. Rituximab was administered as a part of the first line therapy for 26 patients and as maintenance therapy for 37. The median and mean number of previous in-hospital SC injections was 1 (range 1 to 10) and 3.1, respectively. A total of 174 injections were performed at home (median per patient: 4, range: 1 to 10). Few side effects were notified; late-onset neutropenia (n=3), upper and lower respiratory tract infections (n=4), P. jirovecii pneumonia (n=1), grade 3 diarrhea of unknown etiology (n=1), incidental cancers (n=2) and one non-related death. Finally, 4 patients required hospitalization due to complication. One patient went back to in-hospital administration because of bone pain and local skin reaction related to injection. In France, the cost of care is a flat fee determined by the Health authorities which is 1049 euros for standard one-day hospitalization in ambulatory unit of public hospital, 233 euros for private and 201 euros for public one-day home hospitalization. In our cohort, home administration is associated with a cost saving of 146 592 euros (842 euros per injection, 3758 euros per patient), to which we must add patients' transport cost.ConclusionOur study showed that home administration of subcutaneous rituximab is feasible, safe, and well tolerated, leading to an alternative to standard hospitalization. Moreover, amount of cost saving should justify promotion of home administration by Health authorities. If quality of life is improved by home administration it must be confirmed by prospective studies. Currently, home administration of SC rituximab but also brentuximab vedotin, eculizumab and more recently daratumumab is part of our standard of care. DisclosuresWolfromm:Janssen: Consultancy. Delarue:Roche: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Gilead: Consultancy, Honoraria.

Primary Vitreoretinal Lymphoma Therapy Monitoring: Significant Vitreous Haze Reduction After Intravitreal Rituximab.

Intravitreal rituximab is an off-label treatment option for primary vitreoretinal lymphoma (PVRL). The objective of this study was to monitor the therapeutic response and safety profile of intravitreal rituximab in a cohort of PVRL patients. In this retrospective, uncontrolled, open label, multicentre study, 20 eyes from 15 consecutive patients diagnosed with PRVL received at least one intravitreal injection of 1mg in 0.1ml rituximab. Biodata of the PVRL patients was recorded as well as visual acuity and vitreous haze score immediately before rituximab intravitreal injection and at follow-up examinations. Intravitreal rituximab safety data was also recorded. Additional rituximab injections were made during control visits on a pro re nata (PRN) regime using increased vitreous haze to indicate recurrence. There was significant vitreous haze reduction (p=0.0002) followed by significant improvement of visual acuity (mean best visual acuity before therapy 0.57 logMAR, after therapy 0.20 logMAR (p=0.0228) during the follow-up time up to 4 years. Only mild ocular side effects were reported. Median follow-up time was 565 days (range, 7-1253 days). Intravitreal rituximab therapy shows promising PVRL regression without any severe side effects. Although our clinical data support rituximab as intravitreal therapy in PVRL disease, further study is warranted.

No Early Effect of Intrathecal Rituximab in Progressive Multiple Sclerosis (EFFRITE Clinical Trial).

Background The progressive phase of multiple sclerosis (MS) is characterized by an intrathecal (IT) compartmentalization of inflammation, involving B-cells within meningeal follicles, and resisting all the available immunosuppressive treatments. A new therapeutic paradigm may be to target this inflammation by injecting immunosuppressive drugs inside the central nervous system compartment. Methods We designed a single-center, open-label, randomized, controlled, phase II study designed to evaluate the safety and efficacy of IT rituximab in progressive MS (EFFRITE trial; ClinicalTrial Registration NCT02545959). Patients were randomized into three arms (1 : 1 : 1): control group, IT rituximab (20 mg, IT) group, and intravenous+IT (IV+IT) group. The main outcome was a change in levels of CSF biomarkers of inflammation (osteopontin). Secondary outcomes were changes in levels of CSF biomarkers of axonal loss (neurofilament light chain) and clinical and MRI changes. Results Ten patients were included (2 : 4 : 4). No adverse event occurred. OPN level remained stable in CSF at each time point, whereas NFL had slightly decreased (-8.7%) at day 21 (p = 0.02). Clinical parameters remained stable and leptomeningeal enhancements remained unchanged. Conclusion Clinical outcome and biomarkers of inflammation were not dramatically modified after IT injection of rituximab, probably due to its limited efficiency in CSF. Drug issues for future studies are discussed.

Hypogammaglobulinemia during Rituximab Maintenance after Transplantation Is a Surrogate Marker for Disease Control in Patients with Mantle-Cell Lymphoma, an Analysis from the LyMa Trial

Hypogammaglobulinemia during Rituximab Maintenance after Transplantation Is a Surrogate Marker for Disease Control in Patients with Mantle-Cell Lymphoma, an Analysis from the LyMa Trial

Intralesional injection of biosimilar rituximab in recalcitrant mucocutaneous lesions of patients with pemphigus vulgaris: A pilot study.

The efficacy of intravenous rituximab (RTX) in patients with pemphigus have been shown in the previous studies. The study aimed to investigate the effectiveness of intralesional injection of RTX in the healing of pemphigus lesions, with lower doses and probable better safety profile than intravenous RTX. Eleven Pemphigus patients with recalcitrant lesions received two intralesional injections of biosimilar RTX, 5 mg/cm2 . During 6 months follow-up, Pemphigus Disease Area Index, the patients' satisfaction, quality of life, the disease activity, the number and size of lesions, the anti-desmoglein (Dsg) 1 and 3 antibodies and the count of CD4+ and CD19+ cells were assessed. All patients were in partial remission on therapy. The absolute count of CD19+ B cells showed a statistically significant decline (P = .006). The percentage of CD4 + T lymphocytes increased 2 weeks after injection and decreased 2 weeks later (P = .01). The average number and size of lesions decreased. The concentration of anti-Dsg 3 antibody decreased insignificantly during the study. The severe pain during the injection was considered as the main complication. At the end of the study, two patients were in complete remission on therapy, and the other nine remained in partial remission on therapy. Few side effects resulting from intralesional injection of RTX and enhanced quality of life of the patients were considered as the valuable achievements of this study. The results showed that although a low dose of RTX leads to a significant decrease of CD19+ B lymphocytes, it did not show parallel clinical effectiveness.

Rituximab Hypersensitivity: From Clinical Presentation to Management

Rituximab is a chimeric monoclonal antibody (mAb) against CD20 molecule which is expressed on human B cells. It has been used for the treatment of various lymphoid malignancies, lymphoproliferative diseases, and rheumatologic disorders. Rituximab is generally well tolerated. However, increased use of rituximab has been associated with hypersensitivity reactions (HSRs), which can be classified as infusion-related, cytokine-release, type I (IgE/non-IgE), mixed, type III, and type IV reactions. Immediate infusion-related reactions to rituximab are quite common and decrease in frequency with subsequent infusions. However, in about 10% of patients, severe infusion-related reactions develop, which prevent its use. Some of the immediate infusion reactions are due to a cytokine-release but some reactions raise concerns for type I (IgE/non-IgE) hypersensitivity. Recent studies have shown the presence of serum anti-rituximab antibodies, either represented by the IgG or IgE isotype. In some cases, clinical manifestations of IgE-mediated reactions and cytokine-release reactions partially overlap, which is called a mixed reaction. Classified as Type III reaction, rituximab-induced serum sickness reactions have been reported in patients with autoimmune diseases and hematological malignancies. The classic serum sickness triad (fever, rash, and arthralgia) has been observed in patients mainly with an underlying rheumatologic condition. Severe delayed type IV hypersensitivity reactions including non-severe maculopapular rash to severe reactions such as Stevens–Johnson syndrome and toxic epidermal necrolysis have been rarely reported following rituximab injection. Comprehensive reviews focused on rituximab-induced HSRs are scarce. We aimed to review clinical presentations, underlying mechanisms of rituximab hypersensitivity, as well as management including rapid drug desensitization.

Clinical Experience in a Large Cohort of Patients with Vitreoretinal Lymphoma in a Single Center

ABSTRACT Background/aims: To report our five-year experience on vitreoretinal lymphoma (VRL) as a single-center tertiary hospital. Methods: The ophthalmic, cytopathology, and onco-hematologic records of patients with VRL consecutively seen from 2014 to 2019 were reviewed. Results: Fifty-nine eyes of 31 patients with large B-cell VRL were included. Eighty-one percent has developed central nervous system lymphoma at the end of follow-up. Several different imaging findings were noted, including vitritis, leopard spot appearance, Bruch’s membrane/RPE infiltrations, and ellipsoid zone disruption. A variable combination of MYD88-L265P mutation in the aqueous and/or in the vitreous and positive cytology/histology allowed to reach a definite diagnosis in all the patients. Therapies included intravitreal injections of methotrexate and rituximab, systemic chemotherapy, pan-encephalic radiotherapy, and hematopoietic stem cell transplantation. Conclusion: No definite guidelines exist for VRL management. It is crucial to collect as much data as possible from tertiary referral hospitals, which suitably manage a conspicuous number of VRL patients.

Burkholderia sepsis mimicking flare of ANCA-associated vasculitis: A rare presentation

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune condition that primarily targets small to medium sized vessels in multiple organ systems, with sinonasal, pulmonary and renal involvement being common. The present case study discusses a known case of ANCA associated vasculitis, type 2 diabetes and hypertension, who presented with altered sensorium and weakness of the left side of the body. Few months before the onset of symptoms, the patient received rituximab injection for treating cutaneous panniculitis and high pANCA titers. MRI of brain and CECT of chest were suggestive of vasculitis and blood culture showed the growth of Burkholderia cepacia. She was treated with broad spectrum antibiotics and other supportive treatment. Despite all the efforts including ionotropic and ventilator supports, the patient succumbed to the infection.

Rituximab in maintaining remission in adults with podocytopathy

This was a prospective study carried out at a tertiary care centre in India between January 2014 and June 2019. Adults between 16 and 60 years with SD, frequently relapsing (FR), and SR nephrotic syndrome (NS) due to podocytopathy received rituximab in a CD19-targeted approach. Percentage of patients who were in remission at 6 and 12 months. Secondary outcome: Percentage of patients in remission at the last follow-up, rituximab dose and adverse events of rituximab therapy. Fifty-three adults with SD/FR/SR NS received CD19-targeted rituximab. The median age at the time of first rituximab injection was 30.09 ± 13.21 (16.53) years. At the time of first rituximab infusion, all patients were in remission with steroids and/or calcineurin inhibitors (CNIs). Fifty (94.33%) patients were in remission at the end of 6 and 12 months and the last follow-up (median: 36 months). The mean total dose of rituximab at 1 year was 788.7 ± 128.1 (6 001 100) mg. At last follow-up (median 36 months), 42 (79%) patients did not require any additional CNI or steroids therapy. No serious adverse events to rituximab were noted. CD19-targeted rituximab therapy is safe and efficacious in the management of SD/SR adult podocytopathy. Also, rituximab is effective in maintaining remission in treatment naïve adult SD or FR podocytopathy.

P0202FIRST REAL-LIFE DATA OF PATIENTS TREATED FOR THROMBOTIC THROMBOCYTOPENIC PURPURA FROM THE FRENCH THROMBOTIC MICROANGIOPATHIES NETWORK

Abstract Background and Aims Caplacizumab, a bivalent Nanobody, targets the A1 domain of von Willebrand Factor, inhibiting the interaction between ultra-large vWF and platelets in the treament of Acquired Thrombotic Thrombocytopenic Purpura (aTTP). Results of the Phase 3 HERCULES study confirm that treatment with caplacizumab reduces the time to platelet count response, resulting in faster resolution of aTTP. Treatment with caplacizumab also resulted in a highly clinically meaningful reduction in aTTP-related death, recurrence of aTTP, or a major thromboembolic event during study drug treatment. Data from clinical practice confirming the clinical trial data is still scarce. We report here the first real world evidence collected in the French thrombotic microangiopathies network. Method Patients with an acute episode of aTTP were included in an observational prospective multicentric study. The diagnosis of aTTP was done according to the French score (platelet count &amp;lt; 30 g/l and serum creatinine&amp;lt; 200µmol/l) or ADAMTS13 activity if available. Adult patients were proposed to be treated with daily plasma exchange (PE) in addition to corticosteroid and frontline rituximab plus early initiation of caplacizumab. PE was stopped after 2 days of platelet count normalization. Results Fifty patients (36 females, median age of 46 years old) were treated for aTTP. 30 patients (60%) had cerebral involvement and 13 (26%) had cardiac involvement. Cardiac troponin I was above upper normal value for 61% of patients. Before treatment, median platelet count was 16 g/l and median serum creatinine was 86 µmol/l. Three initial clinical suspicions of aTTP were finally diagnosed as HUS (2 patients) or vitamin deficiency (1 patient) resulting in the stop of treatment. A median number of 6 plasma exchanges was administered (min:3 - max:16). 375mg/m rituximab injections (3 to 4 for 35/43 patients with reported data) were mostly initiated within 3 days after the first plasma exchange. Caplacizumab treatment was initiated early (37/42 patients with reported data within 2 days after 1st plasma exchange) with a total median duration of treatment of 33 days (min:18 - max:35). The median platelet count normalization was 5 days (min:4 - max:6). 6/41 (14,6%) experienced exacerbations. No deaths and no patients refractory to therapy were reported. Eight adverse events related to caplacizumab therapy were reported, all with good outcomes. Conclusion Concomitant start of additional treatments allow to target severe ADAMTS13 deficiency and platelet aggregation which causes early mortality. The clinical French score seems useful in clinical practices.

Treatment of MALT lymphoma of the conjunctiva with intralesional rituximab supplemented with autologous serum

AbstractPatients with indolent conjunctival lymphomas exhibit good prognosis, with exceptional cases of dissemination, and are suitable candidates for intralesional therapies. We report the first prospective phase 2 trial using intralesional rituximab supplemented with autologous serum in adults with relapsed/refractory indolent CD20+ lymphoma of the conjunctiva (NCT01514344). Patients received 4 weekly intralesional injections of rituximab, followed by 6 monthly injections; 500 μL of autologous serum was added to rituximab in patients with lymphoma unresponsive to weekly doses. Safety, activity, and antitumor effect of autologous serum were investigated. Twenty patients with mucosa-associated lymphoid tissue (MALT)–type lymphoma were enrolled. Tolerability was excellent, with only 3 mild local reactions. After weekly injections, 11 patients achieved tumor regression, 8 had stable disease, and 1 experienced progressive disease; 9 patients received autologous serum, with response improvement in 4 cases (3 complete responses, 1 partial response). At the end of treatment, 12 patients achieved a complete remission, and 1 achieved a partial response, with an overall response rate of 65% (95% confidence interval, 45-85). At a median follow-up of 42 months (range, 10-78), 12 patients remain relapse free, with 5-year progression-free survival and time-to-next-treatment rates of 59% ± 11% and 69% ± 11%, respectively. Three patients with local relapse were retreated with intralesional rituximab and serum; 2 achieved a complete response that lasted 25+ and 38+ months. Thus, intralesional rituximab is a safe and active therapy in patients with relapsed conjunctival MALT lymphoma. The addition of autologous serum improves response in some cases. Retreatment of local relapses can result in a second durable remission.

Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates.

Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments.

A long-term follow-up of rituximab treatment in 20 Chinese patients with neuromyelitis optica spectrum disorders

BackgroundRituximab has been recommended as the first-line therapy for neuromyelitis optica spectrum disorders (NMOSD); however, its regimen is yet to be optimised. We aimed to present our experience of treating adult Chinese patients having NMOSD with low-dose rituximab, and to further investigate its efficacy and safety in a long-term follow-up. MethodsTwenty adult Chinese patients with NMOSD, who had received rituximab injections, were retrospectively analysed, and followed up over a long time in our hospital. Efficacy was evaluated mainly by the change in expanded disability status scale and annual relapse ratio before and after rituximab therapy. Safety was reflected by the incidence and severity of side effects. ResultsRituximab regimens, including doses and intervals, varied widely across patients. The median dose was 500 mg, ranging from 100 mg to 1000 mg. The median interval was 6.1 months, ranging from 2 months to 18 months. After rituximab therapy, the median EDSS was stable, whereas median ARR decreased by 90%. Of the 20 patients, 9 suffered from 11 relapses, with relapse-free rate of 55%. Six relapsing cases occurred in less than 6 months from the preceding rituximab injection. Seven cases occurred without CD19+ B cell repopulation. There were 4 cases of infection, including lung and urinary infection; severity ranged from mild to severe across the patients. ConclusionsWe confirmed the long-term efficacy and safety of low-dose rituximab in adult Chinese patients with NMOSD. We recommend monitoring of B cell repopulation to instruct individualised regimens for patients with NMOSD in clinical practice.