Search

PurposeMethodsResultsConclusionWe report three cases of occlusive vasculitis following intravitreal rituximab therapy for biopsy-proven primary vitreoretinal lymphoma (PVRL), one of which was following an injection of the biosimilar Riabni (rituximab-arrx, AmGen) and two of which were following an injection of Rituxan (rituximab, Genentech).Case series.Three cases of occlusive vasculitis confirmed with fluorescein angiography are reported 5 days, 8 days, and 3.5 weeks following intravitreal injection of rituximab. The initial vision was poor (20/500, 20/150, and light perception), but vision recovered to baseline in two cases, and remained poor in the case of combined artery and vein occlusion.Occlusive vasculitis is a rarely reported but potential complication of intravitreal rituximab therapy in patients who have been previously treated with the agent and may have delayed onset. A low threshold for fluorescein angiography as a diagnostic test for post-injection vision loss and prompt treatment with topical and/or oral steroids should be considered. [ABSTRACT FROM AUTHOR]

AbstractLenalidomide (LEN) and rituximab (RTX) have independently improved progression-free survival (PFS) in CLL, leading to interest in use of LEN + RTX (R2) following induction chemoimmunotherapy. Patients with previously untreated CLL received bendamustine + RTX (BR) for 6 cycles, then 24 cycles of R2. LEN dosing was 5–10 mg daily; RTX was given odd cycles (12 doses). The primary endpoint is PFS; secondary endpoints are response and overall survival. Thirty-six patients enrolled, median age 64.5 years. Twenty-nine received R2; 12 completed a full course R2 (33.3%), 5 completed R2 with premature discontinuation of LEN. Dose reductions/holds were most often for neutropenia. Complete response was achieved in 33.3%. After median >4 years follow-up, 2-year and 3-year PFS were 86.1% and 69.4%. Five-year overall survival was 92.3%. R2 maintenance may improve PFS after BR induction, and a lower dose of 5 mg/day and ≤1 year of R2 may be most tolerable (NCT00974233). [ABSTRACT FROM AUTHOR]

We present a case of an uncommon presentation of IgG4-related ophthalmic disease (ROD). A 58-year-old female presented with unilateral acute anterior uveitis of the right eye, which progressed to scleritis with the development of an associated orbital mass despite treatment with oral glucocorticoid. Initial histopathology of an orbital biopsy was non-diagnostic and continued progression of the disease lead to complete loss of vision in the right eye. The development of uveitis in the previously unaffected left eye led to the decision for enucleation of the right globe and further orbital biopsy. Histopathology revealed features supporting IgG4-related ophthalmic disease. Oral glucocorticoid therapy failed to induce remission, and rituximab therapy was initiated, leading to a rapid resolution in her symptoms. Other cases with a similar presentation report a poor visual prognosis, highlighting the need for prompt diagnosis and treatment of uveitis associated with signs of orbital or scleral involvement. [ABSTRACT FROM AUTHOR]

Lenalidomide and rituximab (R2) is an effective frontline treatment for patients with indolent B-cell non-Hodgkin lymphoma (iNHL). We investigated the safety and efficacy of addition of the proteasome inhibitor ixazomib to R2 for treatment of iNHL through a phase I/II clinical trial for high-risk patients. Twenty patients were enrolled, 18 were treated. The target dose of ixazomib 4 mg weekly was achieved during dose escalation. The most common treatment-related adverse events (AEs) were low grade gastrointestinal, rash, neuropathy, and myalgia/arthralgia. There were 33% grade 2 and 17% grade 3 infections. With median follow-up of 5.2 years, four patients discontinued treatment due to lymphoma progression. Best overall response rate (ORR) was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. Kaplan-Meier estimates of progression free and overall survival (OS) were 73% and 87% at 36 months, respectively. R2 can safely be combined with ixazomib for treatment-naïve iNHL patients. [ABSTRACT FROM AUTHOR]

AbstractWe report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event-free survival (EFS) or overall survival (OS). With a median follow-up of 7.8 years (range: 0.40–18.8), eight patients have experienced disease relapse (5.8%), 4/111 with newly diagnosed HCL (3·6%) and 4/10 with HCLv (40%) (p = 0.002). The 10-year EFS and OS rates were 86.7% and 91.1%, respectively. Grade 3 adverse events were observed in 28 participants (20·1%), mostly due to infections. Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed settings. [ABSTRACT FROM AUTHOR]

Objective: To describe the reversal of peripheral iris depigmentation associated with Vogt-Koyanagi- Harada (VKH) disease. Methods: A retrospective report of two cases. Results: Both patients were diagnosed with a chronic recurrent VKH disease and developed bilateral peripheral iris depigmentation (BPID). The first patient is an 8-year-old girl who was treated with systemic corticosteroids, methotrexate and adjuvant rituximab infusions that induced complete remission of uveitis and reversal of peripheral iris depigmentation at the last follow-up. The second was a 6-year-old who was treated with topical and systemic corticosteroids and oral methotrexate that induced complete remission of uveitis and reversal of peripheral iris depigmentation at the last follow-up. Conclusions: Adequate control of uveitis associated with chronic recurrent VKH disease with appropriate immunomodulatory agents and perhaps adjuvant rituximab can reverse BPID and improve the outcomes. [ABSTRACT FROM AUTHOR]

AbstractParsaclisib, a potent and highly selective phosphoinositide 3-kinase δ inhibitor, has shown clinical activity in relapsed/refractory (R/R) B-cell lymphoma. The phase 1 CITADEL-112 (NCT03424122) study assessed safety and efficacy of parsaclisib in combination with investigator choice standard of care (SOC; rituximab [Treatment A], rituximab plus bendamustine [Treatment B], or ibrutinib [Treatment C]) in 50 patients with R/R B-cell lymphoma. The most common treatment-emergent adverse events included neutropenia (62.5%, 50.0%, and 50.0% of patients in Treatments A, B, and C, respectively); diarrhea (37.5%) and anemia (31.3%) in Treatment A; abdominal pain, asthenia, diarrhea, and nausea (each 33.3%) in Treatment B; and increased alanine and aspartate aminotransferase (each 37.5%) in Treatment C. Objective responses were observed in 13 patients (81.3%) in Treatment A, 10 (55.6%) in Treatment B, and 8 (50.0%) in Treatment C. Parsaclisib combined with SOC therapies had an expected safety profile and promising efficacy in patients with R/R B-cell lymphomas. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionThis study assesses the efficacy of rituximab in the treatment of neuromyelitis optica spectrum disorders (NMOSD).The study initially included 40 patients with NMOSD diagnosed, after excluding patients who did not meet the complete inclusion criteria. Patients in the conventional group received routine clinical treatment, while patients in the study group received additional treatment with rituximab on the basis of the conventional treatment. Baseline data and clinically relevant indicators were collected for all patients, and the efficacy was compared between the two groups.Baseline data were comparable between the two groups (p > 0.05). The EDSS scores after clinical treatment in the study group were lower than those in the conventional group, and the difference in EDSS scores before and after treatment was higher than that in the conventional group (p < 0.05). The difference in visual acuity correction before and after treatment was not significant between the two groups (p > 0.05). Laboratory indicators in the study group after clinical treatment were superior to those in the conventional group (all p < 0.05). The recurrence rate after clinical treatment in the study group was significantly lower than that in the conventional group (p < 0.05). Adverse reactions after clinical treatment in the study group were less than those in the conventional group (p < 0.05).This study found that rituximab demonstrated significant efficacy in the acute attacks and recurrence prevention of NMOSD, emphasizing its relatively good safety and tolerability. It highlights the potential of rituximab in treating NMOSD and provides valuable insights for future disease management. [ABSTRACT FROM AUTHOR]

Cell therapies comprise one of the most important advances in oncology. One of the biggest challenges in the early development of cell therapies is to recommend safe and feasible doses to carry forward to middle development. The treatment involves extracting cells from a patient, expanding the cells and infusing the cells back into the patient. Each dose level being studied is defined by the number of cells infused into the trial participant. The manufacturing process may not generate enough cells for a given patient to receive their assigned dose level, making it infeasible to administer their intended dose. The primary design challenge is to efficiently use accumulated data from participants treated away from their assigned dose to efficiently allocate future trial participants and recommend a feasible maximum tolerated dose (FMTD) at the study conclusion. Currently, there are few available options for designing and implementing Phase I trials of cell therapies that can incorporate a dose feasibility endpoint. Moreover, the application of these designs is limited to a traditional dose-finding framework, where the dose-limiting toxicity (DLT) endpoint is observed in early cycles of therapy. This paper presents a novel phase I trial design for adoptive cell therapy that simultaneously accounts for dose feasibility and late-onset toxicities. We apply our design to a phase I dose-escalation trial of Rituximab-based bispecific activated T-cells combined with a fixed dose of Nivolumab. Our simulation results demonstrate that our proposed method can reduce trial duration without significantly hindering trial accuracy. [ABSTRACT FROM AUTHOR]

Patients with asymptomatic follicular lymphoma (AFL) are candidates for observation or immunotherapy. Given the effectiveness of radiation therapy in FL, another option is 90Yttrium-ibritumomab tiuxetan radioimmunotherapy (RIT). We conducted a trial where untreated AFL patients were randomized to rituximab 375 mg/m2 weekly × 4 or rituximab 250 mg/m2 days 1, 8, and 0.4 mCi/kg (maximum 32 mCi) of RIT day 8. Twenty patients were enrolled before the study was halted due to unavailability of RIT. The ORR for rituximab and RIT were 90% and 80%, respectively; the CR rate at 6 months was 30% and 60%, respectively. After a median follow-up of 67 months, eight patients have progressed—three in the rituximab arm and five in the RIT arm and five have required systemic therapy. All patients remain alive. Both agents are highly active for AFL. The 1-week treatment with RIT and sparing of T-cells make combination therapy with newer agents attractive. [ABSTRACT FROM AUTHOR]

We report on outcomes of 111 patients with treatment naïve Waldenström macroglobulinemia (TN WM) treated with frontline bendamustine–rituximab (BR) (n = 57) or rituximab–cyclophosphamide–vincristine–prednisone (RCVP) (n = 54). Median follow-up was 60.7 months (range 1.9–231.6). Median progression-free survival (PFS) was 60.5 months (95% CI 47.6–73.4) for BR and 79.0 months (95% CI 31.3–126.8) for RCVP (p =.96). Median overall survival (OS) was not reached for BR and 153.4 months (95% CI 114.5–192.4) for RCVP (p =.37). While overall and major response rates did not differ between treatment groups, BR had numerically higher rate of very good partial response or better response (51% vs. 37%, p =.30) and complete response (26% vs. 13%, p =.13). RCVP confers comparable outcomes to BR in a real-world population of TN WM patients and remains an effective regimen, particularly when tolerance or frailty is an issue, or in resource-limited settings. [ABSTRACT FROM AUTHOR]

This dose-finding study evaluated safety of venetoclax plus Bendamustine-Rituximab-Ibrutinib in relapsed/refractory MCL. Six 28-day cycles were administered in a 3 + 3 dose-escalation design. Dose level 1 (DL1) included Bendamustine 90 mg/m2 on day 1-2, Rituximab 375 mg/m2 on day 1, and Ibrutinib 560 mg daily. Venetoclax was dosed with ramp-up and at 400 mg starting in Cycle 2 for 5 days. The most common adverse events were thrombocytopenia (80%), constipation (60%), and fatigue (60%). Rare hematologic grade 3-4 AEs, 1 dose-limiting toxicity at DL1 (prolonged grade 3 thrombocytopenia), and delayed hematologic toxicity were observed. DL-1 with Bendamustine dose-reduced to 70 mg/m2 (n = 3) revealed no significant toxicity. The overall and complete response rates were both 80% (8/10). This study underscored that venetoclax combined with chemoimmunotherapy is complicated by hematologic toxicity, limiting future development. Although a maximum tolerated dose was not formally established given early study closure, this study demonstrated preliminary tolerability and efficacy of Bendamustine-Rituximab-Ibrutinib-Venetoclax at DL-1. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo report an uncommon, isolated presentation of bilateral choroidal detachments in a patient diagnosed with P-ANCA-associated vasculitis and to highlight the importance of an inflammatory work-up in such cases.Case report.A 70-year-old male with a past medical history of autoimmune hepatitis presented with a sudden decrease in vision in both eyes. Over the course of the previous decade, he had experienced recurrent attacks of episcleritis, which were successfully managed with topical corticosteroid eye drops. The patient was diagnosed with bilateral detachments without accompanying scleritis or intraocular inflammation. Inflammatory markers revealed high P-ANCA and anti-MPO levels, confirming the diagnosis of P-ANCA-associated vasculitis. Treatment with systemic rituximab and corticosteroids led to the resolution of the choroidal detachment in both eyes. A 40-month follow-up confirmed the sustained resolution of the detachments.Choroidal detachment without other extraocular/intraocular inflammation can be associated with P-ANCA-associated vasculitis, a previously under-reported link. It is important to consider an inflammatory work-up for patients presenting with choroidal detachment to rule out conditions like P-ANCA-associated vasculitis. [ABSTRACT FROM AUTHOR]

Rituximab, anti-CD20 monoclonal antibody, has broad clinical application. The aim of this study is to compare the safety and cost of the original reference rituximab (MabThera) and its biosimilar (Riximyo). This retrospective analysis of 262 patients receiving Riximyo in the Department of Hematology of Wroclaw Medical University in Poland from the period of 1 October 2020 to 21 June 2021 focused on infusion-related reactions (IRRs), which occurred in 4,96% of patients (N = 13). 109 patients (41,6%) had previously been treated with the reference drug and 2 IRRs were reported after switching therapy. During the study period, after biosimilar introduction, the cost of rituximab decreased by 41%. Rixmyo while maintaining similar safety profile is much more cost-effective. [ABSTRACT FROM AUTHOR]

PurposeMethodResultConclusionTo report a patient with bilateral scleritis who was initially treated for infectious scleritis, and subsequently diagnosed as granulomatosis with polyangiitis (GPA).Retrospective chart review.A 48-year-old female with a known history of diabetes presented with pain, redness, and blurring of vision in the right eye. She was diagnosed as scleritis with retinal detachment and underwent vitrectomy, with silicone oil tamponade and intravitreal injections of antibiotics, and antifungal agents. She presented with active scleritis with additional multiple pus points. Several scleral biopsies failed to yield any microorganism and finally, the painful blind eye was enucleated. The enucleated specimen grew gram-positive bacteria which were identified as Staphylococcus arlettae by polymerase chain reaction (PCR)-based sequencing of the 16S rRNA gene. Nine months after the onset of symptoms in the right eye, the patient developed necrotizing scleritis in the left eye. Laboratory investigation revealed a positive cytoplasmic- anti-neutrophil cytoplasmic autoantibody, which was previously negative during the right eye involvement. She was diagnosed with GPA by a rheumatologist and treated accordingly.Retinal detachment may be associated with scleritis, and ANCA testing may not detect GPA in its early stages. Once infection has been excluded, clinicians should not be afraid to use high-dose immunosuppression instead of surgery to treat retinal detachment associated with scleritis. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma that frequently becomes chemoresistant over time. The distinct mechanisms of ibrutinib and lenalidomide provided a judicious rationale to explore the combination with anti-CD20 immunotherapy. In this phase 1b study (NCT02446236), patients (n=25) with relapsed/refractory MCL received rituximab with escalating doses of lenalidomide (days 1–21) and ibrutinib 560mg (days 1–28) of 28-day cycles. The MTD for lenalidomide was 20mg; most common grade ≥3 adverse events were skin rashes (32%) and neutropenic fever (24%). The best ORR was 88%, CR rate was 83%, and median duration of response (DOR) was 36.92months (95% CI 33.77, 51.37). Responses were seen even in refractory patients or with high-risk features (e.g. blastoid variant, TP53 mutation, Ki-67>30%). R2I was safe and tolerable in patients with R/R MCL. [ABSTRACT FROM AUTHOR]

The association between T-cell large granular lymphocytes (T-LGL) and ITP is uncertain. The aims of this study were to determine the prevalence of T-LGL in patients with ITP and to describe its association with ITP disease severity. We analyzed flow cytometry results for T-LGL (using a threshold of 0.3 x109 or greater cells/L) or positive T-cell receptor clonality in patients with ITP and nonimmune thrombocytopenia. Descriptive statistics were used to characterize the association between T-LGL and ITP, response to ITP treatments (rituximab and splenectomy) and response to T-LGL treatment. Among ITP patients, 14.3% (13/91) had evidence of a T-LGL population compared to 10.3% (3/29) of patients with non-immune thrombocytopenia. ITP patients with T-LGL had lower nadir platelet counts (2 vs. 47 × 109/L) and received more ITP treatments (median 6 vs. 3) than ITP patients without T-LGL. Response to rituximab was observed in 14.3% (1/7) of ITP patients with T-LGL and 54.5% (6/11) without T-LGL. Response to splenectomy was observed in 25% (2/8) with T-LGL and 56.2% (9/16) without T-LGL. Four patients with ITP and T-LGL received treatment for T-LGL with methotrexate; none had an improvement in platelet count levels. T-LGL may appear in patients with ITP, and the meaning of this finding remains unclear; however, for some patients, the presence of abnormal T-LGL may indicate a more severe form of ITP that tends to be less responsive to therapy. In this cohort, treatment of T-LGL with methotrexate did not improve platelet counts in the few patients who were treated. [ABSTRACT FROM AUTHOR]

The emergence of rituximab biosimilars offers the prospect of significant savings to the healthcare system. However, these drugs have never been evaluated for treating immune thrombocytopenia (ITP). This was an observational, matched study. We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from the historic ITP-ritux registry. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product. Response status was defined according to international criteria. We included 107 patients; 55 receiving Rixathon™ and 52 Truxima™. Three months after the first infusion of rituximab biosimilars, the overall response rate was 47/74 (63.5%) versus 76/142 (53.5%) for the matched controls receiving the reference product (p = .13). The 3-month overall response rate was 76.5% for Rixathon™ versus 51.5% for the matched control group (p = .01) and 21/40 (52.5%) for Truxima™ versus 41/74 (55.4%) for the matched controls (p = .81). For non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product. Rituximab biosimilars seemed safe and effective for ITP treatment. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to evaluate whether anti-glycoproteins (GPs) autoantibodies can be used as predictors of response to high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) patients. One-hundred twenty-six ITP patients were included and retrospectively analyzed, 66.7% of anti-GPIb/IX and 65.9% of anti-GPIIb/IIIa autoantibodies. Results showed that overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at 4 weeks (OR: 73.8% vs. 47.6%, CR: 50.0% vs. 26.2%; P < 0.05) and 6 months (OR: 71.4% vs. 45.2%, CR: 42.9% vs. 25.0%; P < .05). Furthermore, patients with anti-GPIb /IX single-positivity exhibited higher resistance to DXM-RTX than patients with anti-GPIIb/IIIa single-positivity at 4 weeks (OR: 37.5% vs. 78.3%; P < .05) and 6 months (OR: 29.2% vs. 78.3%; P < .05). Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies and megakaryocytes were associated with the OR rate of patients at both 4 weeks and 6 months, and anti-GPIb/IX autoantibodies at 4 weeks represented the only significant factor affecting OR rate with DXM-RTX (F = 9.128, P = .003). Therefore, platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX in ITP patients. [ABSTRACT FROM AUTHOR]

It remains unclear whether the low amount of SMPDL-3b required for rituximab binding is the cause of treatment resistance in patients with treatment-resistant nephrotic syndrome with advanced podocyte injury. Given the limited number of studies on the relationship between rituximab and SMPDL-3b, this study was conducted to assess whether SMPDL-3b levels in pretreatment renal biopsy specimens can be used to predict the clinical effectiveness of immunosuppressive drugs, especially rituximab, in children with nephrotic syndrome. Kidney biopsy specimens from 44 patients diagnosed with idiopatic nephrotic syndrome were analyzed using immunohistochemical staining with an anti-SMPDL-3b antibody and real-time polymerase chain reaction (PCR) for SMPDL-3b mRNA expression. We showed that SMPDL-3b mRNA expression and anti-SMPDL-3b antibody staining did not differ significantly between the patient groups with different responses to immunosuppressive therapies. Our results suggest that SMPDL-3b may actually be an indicator of disease progression rather than a marker for predicting response to a particular immunosuppressive agent. [ABSTRACT FROM AUTHOR]

Polatuzumab vedotin (Pola) was approved for first-line and relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in many countries. This means that retreatment with Pola for r/r DLBCL could be considered after first-line Pola treatment; however, there is currently no evidence on the effectiveness of Pola-retreatment. To address this, we established two Pola-resistant cells from DLBCL cells (SU-DHL-4 and STR-428) and evaluated the combination efficacy of Pola plus rituximab (Rit), the key component of DLBCL therapy. MDR1 overexpression and decreased Bim expression were suggested to be the resistant mechanisms to Pola in Pola-resistant SU-DHL-4 and Pola-resistant STR-428, respectively. In these cells, Pola significantly increased Rit-induced CDC sensitivity either with increased MAC formation or reduced Mcl-1 expression. Additionally, treatment with Pola + Rit significantly enhanced antitumor activity in Pola-resistant STR-428 xenograft mouse models. Based on these results, Pola + Rit retreatment could have preserved efficacy because of the effect of Pola on sensitizing cells to Rit. [ABSTRACT FROM AUTHOR]

The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/– interferon). [ABSTRACT FROM AUTHOR]

The treatment of refractory nephrotic syndrome (RNS) is full of challenges and the role of rituximab (RTX) is not well-established, thus this study aims to demonstrate the role of RTX in RNS. This was a multicenter retrospective study of all adult patients receiving RTX for RNS. Patients enrolled were divided into two groups according to pathological pattern: 20 patients as a group of podocytopathy (including minimal change disease [MCD] and focal and segmental glomerulosclerosis [FSGS]), and 26 patients as membranous nephropathy (MN) group. The remission rate, relapse rate, adverse effects, and predictors of remission were analyzed. A total of 75 patients received RTX for RNS and 48 were available for analysis after exclusion criteria. No significant difference in the remission rate at 6 or 12 months was observed between the MCD/FSGS and MN cases (p > 0.05). The median duration of the first complete remission (CR) was 1 month in the podocytopathy group and 12.5 months in the MN group. Three relapses were associated with infection as the ultimate outcome, and 6 out of 48 remained refractory representing a response rate of 87.5% in RNS. Clinical predictors of cumulative CR were estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and mean arterial pressure (MAP) ≤103 mmHg at the beginning of therapy in patients with MN. No serious adverse effects were reported. RTX appears to be effective in RNS across various clinical and pathological subtypes, exhibiting a low relapse rate and minimal significant side effects in the majority of patients. [ABSTRACT FROM AUTHOR]

The role of subcutaneous (SC) rituximab in the efficacy and safety to non-Hodgkin lymphoma (NHL) is not clear enough. The purpose of this study was to conduct a systematic review and meta-analysis, to assess the efficacy and safety of subcutaneous rituximab to NHL. A full-scale search was carried out based on the set search terms in PubMed, Web of Science, Embase and Cochrane CENTRAL until 12 October 2022 to identify relevant studies of subcutaneous rituximab for NHL. The efficacy and safety outcomes included complete response (CR) plus unconfirmed complete response (CRu), adverse events (AEs), grade ≥3 AEs, serious adverse events (SAEs), administration-related reactions (ARRs), adverse reaction rates. From a total of 758 studies, 9 trials were eligible. The CR/CRu of patients with NHL receiving SC rituximab was 57%, 55% for Diffuse large B-cell lymphoma (DLBCL) and 54% for Follicular lymphoma (FL). The meta-analysis performed on safety demonstrated that AEs of NHL patients with SC rituximab was 85%, grade ≥3 AEs was 38%, SAE was 27% and ARR was 33%. The result also showed that SC rituximab had a high risk of neutropenia and nausea. For NHL patients, there is no significant difference in the efficacy between subcutaneous rituximab and conventional therapy, while subcutaneous injection can shorten exposure time in the hospital and reduce the risk of infection. [ABSTRACT FROM AUTHOR]

Relapsed/Refractory Diffuse Large B Cell Lymphoma have a dismal prognosis in need of innovative treatments. This prospective phase 2 study enrolled 32 patients between 2013 and 2017 with Relapsed/Refractory Diffuse Large B Cell Lymphoma treated with Rituximab and Lenalidomide (R2). Median age was 69 years (40–86), 90.1% had received at least 2 prior lines of treatment, 81% were defined as having High Risk disease according to our criteria and ECOG performance status was > 2 in 51.6%. Patients received a median number of 2 cycles of R2 (1–12). With a median follow up of 22.6 months, the objective response rate was 12.5%. Median progression free survival was 2.6 months (95% CI, [1.7–2.9]) and median overall survival was 9.3 months (95% CI, [5.1–Not estimable]). This study therefore did not achieve its primary endpoint and the R2 regimen cannot be recommended in Relapsed/Refractory Diffuse Large B Cell Lymphoma patients with High Risk features. [ABSTRACT FROM AUTHOR]

Zanubrutinib is a highly selective, next-generation Bruton's tyrosine kinase inhibitor. In the phase 3 SEQUOIA trial (NCT03336333), treatment with zanubrutinib resulted in significantly improved progression-free survival compared to bendamustine plus rituximab (BR) in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) without del(17p). The current analysis compared the effects of zanubrutinib versus BR on patients' health-related quality-of-life (HRQoL). In the SEQUOIA trial, patient-reported outcomes (PROs) were assessed at baseline and every 12 weeks (3 cycles) using the EORTC QLQ-C30 and EQ-5D-5L. Descriptive analyses were performed on all the questionnaires' scales and a mixed model for repeated measures was performed using the key QLQ-C30 endpoints of global health status/QoL (GHS/QoL), physical and role functioning, and symptoms of fatigue, pain, diarrhea, and nausea/vomiting at weeks 12 and 24. Compared with BR-treated patients, those in the zanubrutinib arm experienced greater improvements in HRQoL outcomes at both weeks 12 and 24. By week 24, mean change differences (95% confidence interval) between the arms were significant for GHS/QoL (4.9 [0.9, 9.0]), physical functioning (3.8 [0.8, 6.7]), diarrhea (−6.2 [−10.0, −2.5]), fatigue (−4.5 [−8.9, −0.1]), and nausea/vomiting (−4.5 [−8.9, −0.1]); role functioning (4.8 [−0.2, 9.7]) was marginally better in the zanubrutinib arm and there were no differences in pain symptoms (−0.4 [−4.3, 5.1]) between the arms. During the first 24 weeks of treatment, zanubrutinib was associated with better HRQoL outcomes in patients with treatment-naive CLL/SLL without del(17p) compared to BR. The SEQUOIA trial is registered on clinicaltrials.gov as SEQUOIA trial (NCT03336333). [ABSTRACT FROM AUTHOR]

Through narrative, the subjective experience of illness offers a corrective to biomedicine's interpretive grip. Narrative is both process and product and illness narratives, in particular, are examples of embodied research. This ecopathography – drawing upon embodied experiences of treatment and recovery from late stage Non-Hodgkin's lymphoma – enlists Haraway's cyborg and Lupton's digital assemblage in an effort to make broader claims about patient care in the United States, and specifically, the role of technology in healthcare and in the construction of patient identity. A surgically implanted port (facilitating blood draws and the delivery of chemotherapy) and the patient portal (representing the results of those blood draws as well as a medium for communication) provide a foundation for how cyborgian assemblages both assist and trouble the cancer experience. At stake is the fluidity and ambiguity of boundaries (human/machine, human/animal, and physical/virtual) and the management of those boundaries with regard to patient care. [ABSTRACT FROM AUTHOR]

The variability in disease outcome for indolent non-Hodgkin lymphomas (iNHL) and mantle-cell lymphoma (MCL) could be related to single nucleotide polymorphisms (SNPs) in genes that affect immune and inflammatory response. We investigated SNPs that could have a prognostic role for patients receiving bendamustine and rituximab (BR). All samples were genotyped for the IL-2 (rs2069762), IL-10 (rs1800890, rs10494879), VEGFA (rs3025039), IL-8 (rs4073), CFH (rs1065489) and MTHFR (rs1801131) SNPs by allelic discrimination assays using TaqMan SNP Genotyping Assays. We report a long-term follow-up analysis of 79 iNHL and MCL patients that received BR. Overall response rate was 97.5% (CR rate 70.9%). After a median follow-up of 63 months, median PFS and OS were not reached. We report a significant association between SNP in IL-2 (rs2069762) and reduced PFS and OS (p<.0001). We suggest a role for cytokine SNPs in disease outcome, while SNPs seem not related to long-term toxicity or secondary malignancies. [ABSTRACT FROM AUTHOR]

In immunocompromised patients, persistent SARS-CoV-2 viral shedding and relapsing COVID-19 pneumonia have been described. Currently, little is known about the management of persisting COVID-19, and immunocompromised patients are recommended to be treated using antivirals and immunomodulatory therapies at similar doses and durations as the general population. Previous case reports have described treatment with repeated and prolonged courses of remdesivir and some evidence is emerging in the use of nirmatrelvir/ritonavir combination (NMV/r). We describe a patient with recent chemotherapy including rituximab for follicular lymphoma with persisting SARS-CoV-2 infection. Polymerase chain reaction tests (PCR), cycle threshold values and blood SARS-CoV-2 antigen levels were evaluated. The patient presented with persisting SARS-CoV-2 with relapsing COVID-19 pneumonia. The patient was treated successfully with repeated courses of NMV/r without any observed adverse effects. After the third, prolonged course, the patient remained afebrile and PCR negative, and no relapses have been observed four months after the third NMV/r course. Nirmatrelvir-ritonavir could offer a more accessible alternative to remdesivir. Further research and guidelines for persisting SARS-CoV-2 infection in immunocompromised patients are urgently needed. [ABSTRACT FROM AUTHOR]

ALSUntangled reviews alternative and off-label treatments on behalf of people with ALS who ask about them. Here we review rituximab, a drug which specifically depletes B lymphocytes. We show a current lack of evidence for a role of these cells in ALS progression. The one patient we found who described using Rituximab for their ALS found no benefit. Given all this, and the known serious risks of rituximab, we advise against its use as an ALS treatment. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions We report the long-term effect of rituximab (RTX) in scleritis and determine the value of B-cell monitoring for the prediction of relapses.We retrospectively studied 10 patients with scleritis, who were treated with RTX. Clinical characteristics were collected, and blood B-cell counts were measured before the start of RTX, and at various time points after treatment.Clinical activity of scleritis decreased after RTX treatment in all patients within a median time of 8 weeks (range 3–13), and all reached remission. The median follow-up was 101 months (range 9–138). Relapses occurred in 6 out of 10 patients. All relapses, where B-cell counts were measured (11 out of 19), were heralded by returning B cells. However, B cells also returned in patients with long-term remissions.RTX is a promising therapeutic option for scleritis. Recurrence of B cells after initial depletion does not always predict relapse of scleritis. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is a common, indolent small B-cell lymphoma. While the Follicular Lymphoma International Prognostic Index is widely used, reliable prognostic and predictive biomarkers are needed. A recent study suggested that architectural patterns of CD10, BCL6, and Ki67 expression may correlate with progression-free survival (PFS) in FL patients treated with chemotherapy-free regimens. We examined the prognostic and predictive utility of architectural patterns of CD10, BCL6, Ki67, and FOXP1 in 90 patients treated with immunochemotherapy (bendamustine-rituximab [BR] and R-cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP]). We found that high follicular Ki67 (≥30%) was associated with longer PFS in the subgroup of patients treated with R-CHOP but not among those treated with BR. Validation of this biomarker may support routine use of Ki67 as a predictive marker in FL. [ABSTRACT FROM AUTHOR]

Low-density lipoprotein receptor-related protein-6 (LRP6) is overexpressed in various cancers. The small molecule salinomycin sodium inhibits LRP6. We observed a higher proportion of subjects with non-germinal center B (non-GCB) subtypes having high LRP6 expression than those with GCB subtypes by immunohistochemistry. The PCR and Western blot assays demonstrated increased LRP6 expression in non-GCB subtype cells. In addition, CCK-8 assays and transwell cell migration assays revealed that salinomycin sodium exhibited dose- and time-dependent inhibition of proliferation and migration in non-GCB subtype cells. Furthermore, Western blot assays showed that salinomycin sodium decreased the expression of Bcl2, while increasing the expression of Bax. Additionally, salinomycin sodium suppressed LRP6 expression, blocked LRP6 phosphorylation, and inhibited the Wnt/β-catenin and mTORC1 signaling pathways. Our results suggest that LRP6 is highly expressed in non-GCB subtype. Furthermore, salinomycin sodium inhibited LRP6 expression and the Wnt/β-catenin and mTORC1 signaling in non-GCB subtype cells, and displayed potent anticancer activity. [ABSTRACT FROM AUTHOR]

Background: Rituximab (RTX) is considered the first-line treatment for pemphigus vulgaris (PV), which is a B-cell-mediated acquired autoimmune disease. However, no consensus on the optimum dosage has been achieved. Objectives: To investigate the efficacy and safety of low-dose RTX (a single infusion of 500mg) for the treatment of PV, a cohort study was conducted for patients with PV, along with a 12-month follow-up following the administration of RTX. Methods: Patients with moderate or severe PV were divided into group A (low-dose RTX combined with corticosteroids) and group B (corticosteroids alone). Data on complete remission (CR) rates, doses of corticosteroids, cumulative doses of corticosteroids at the third, sixth, and twelfth months, pemphigus disease area index and adverse effects (AEs) were collected. Results: Forty-four patients with moderate or severe PV were enrolled in this study (19 in group A and 25 in group B). Patients treated with low-dose RTX had higher CR rates, lower doses of corticosteroids at the third, sixth, and twelfth months, lower cumulative doses of corticosteroids at the sixth and twelfth months, and fewer AEs than those who received corticosteroids alone. Conclusions: This study indicated that low-dose RTX may be a beneficial and secure therapy option for patients with moderate to severe PV. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is a mature B-cell neoplasm with a mostly indolent course. Genetic hallmark characteristics are Bcl-2 overexpression based on a t(14;18) translocation and additional secondary genetic and epigenetic aberrations. Standard treatment for early-stage patients has curative intent and usually consists of radiotherapy with or without rituximab. In the advanced stage, the main therapeutic focus is on prolonged remissions. Therefore, treatment in asymptomatic patients is usually deferred. Symptomatic patients are subject to immunochemotherapy induction followed by antibody maintenance. Importantly, about one in five patients subsequently experiences a more rapid clinical course, achieving only short remissions with multiple relapses (POD24). In those patients, there is still an urgent need for improved therapeutic options. Accordingly, a plethora of targeted and immunotherapeutic options, including immunomodulatory drugs, small molecule inhibitors, monoclonal antibodies as well as bispecific T-cell engager antibodies and CAR-T cell products have been recently evaluated in such relapsed high-risk patients. [ABSTRACT FROM AUTHOR]

Objective or Purpose Design Subjects, Participants, and/or Controls Results Conclusions To describe sterile endophthalmitis following intravitreal rituximab (Rituxan, Genentech) injection for treatment of vitreoretinal lymphoma (VRL)Retrospective case seriesMedical records of biopsy-proven VRL patients who received intravitreal rituximab (RTX) between January 2011 and December 2021 in Kellogg Eye Center, University of Michigan were reviewed. 3 patients presented with sterile endophthalmitis after the second dose of intravitreal RTX were included.Methods, Intervention, or Testing: Intravitreal methotrexate (400µg/0.1ml) and rituximab (1mg/0.1ml) injections given a week apart, monthly.Main Outcome Measures: Clinical presentation and response to treatment including visual acuity, degree of inflammation and intraocular pressure .All cases had bilateral disease and received the first dose of intravitreal RTX without any side effects. All cases developed bilateral corneal edema with Descemet’s folds, mutton-fat keratic precipitates, anterior chamber and vitreous cells with hazy fundus view approximately within 1 week after the second RTX injection. Intraocular pressures were increased in Cases 2 and 3. Clinical findings improved to baseline with topical corticosteroid therapy within 1 month in all cases, and additional topical antiglaucomatous medication in Cases 2 and 3. Additionally, Case 1 received the third dose of RTX injection to the right eye 1 month after the second injection and repeating dense anterior chamber and vitreous cells developed in 1 day. Her vision decreased to counting fingers from 20/40, and intraocular pressure increased. After topical steroids and antiglaucomatous medications, her intraocular inflammation subsided. Her vision improved to 20/30, and intraocular pressure became normal in the right eye.To our knowledge, this is the first case series documenting sterile endophthalmitis following intravitreal rituximab in vitreoretinal lymphoma. Recognition of sterile endophthalmitis is important in differentiating from vitreoretinal lymphoma recurrence and infectious endophthalmitis. Close observation and topical steroid drops seem to be effective. [ABSTRACT FROM AUTHOR]

A 54-year-old male presented with a three-year history of bilateral upper eyelid and peri-orbital swelling and adult-onset asthma. Histopathology of a left orbital biopsy showed lymphoid follicles with foamy macrophages and Touton giant cells. Clinical, histological and radiological features were consistent with adult-onset asthma and periocular xanthogranuloma. Treatment with rituximab led to a complete clinical and radiological remission. Nine years later, his condition relapsed with a biopsy of the left orbit and lacrimal gland demonstrating features of IgG4-related disease and adult-onset asthma and periocular xanthogranuloma. Immunohistochemistry showed increased numbers of IgG4+ plasma cells (290 per high power field) and an elevated IgG4+/IgG+ plasma cell ratio of 480%. Involvement by both disorders in the orbit and ocular adnexa of a single patient has not previously been reported in the literature, to the best of our knowledge, and suggests a possible aetiologic or pathophysiologic association. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) utilization for early-stage, low-grade follicular lymphoma (FL) is low despite treatment guideline recommendations. We compare treatment trends for early-stage FL in the era of involved-site RT and rituximab. We identified 11,645 patients in the National Cancer Database (NCDB) with stage I–II, grade 1–2 nodal or extranodal FL diagnosed 2011–2017, with median follow-up of 44 months. From 2011 to 2017, RT utilization rates decreased from 33.4% to 22.4%, observation decreased from 65.3% to 49.7%, chemoimmunotherapy increased from 0.5% to 15.0%, immuno-monotherapy increased from 0.6% to 10.2%, and RT + systemic therapy increased from 0.6% to 2.5%. RT utilization remains low in the involved-site RT and rituximab era. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to evaluate whether anti-glycoproteins (GPs) autoantibodies can be used as predictors of response to high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) patients. One-hundred twenty-six ITP patients were included and retrospectively analyzed, 66.7% of anti-GPIb/IX and 65.9% of anti-GPIIb/IIIa autoantibodies. Results showed that overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at 4 weeks (OR: 73.8% vs. 47.6%, CR: 50.0% vs. 26.2%; P < 0.05) and 6 months (OR: 71.4% vs. 45.2%, CR: 42.9% vs. 25.0%; P <.05). Furthermore, patients with anti-GPIb/IX single-positivity exhibited higher resistance to DXM-RTX than patients with anti-GPIIb/IIIa single-positivity at 4 weeks (OR: 37.5% vs. 78.3%; P <.05) and 6 months (OR: 29.2% vs. 78.3%; P <.05). Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies and megakaryocytes were associated with the OR rate of patients at both 4 weeks and 6 months, and anti-GPIb/IX autoantibodies at 4 weeks represented the only significant factor affecting OR rate with DXM-RTX (F = 9.128, P =.003). Therefore, platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX in ITP patients. What is the context? The safety and efficacy of high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) are gradually recognized; however, there still needs to be an adequate clinical trial to predict its efficacy. Autoantibodies against platelet glycoproteins (GPs) are proven to be associated with a variety of therapeutic responses in ITP. Such as anti-GPIb/IX autoantibodies predict poor response to intravenous immunoglobulin G therapy and rhTPO therapy in ITP patients. Therefore, a retrospective study was needed to verify whether anti-GP autoantibodies can expect a response to DXM-RTX therapy in ITP patients. What is new? This study identified that anti-GPIb/IX autoantibodies were a predictive factor for poor response to DXM-RTX in ITP patients. It mainly manifested in the following aspects: (1) Overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at four weeks and six months. (2) Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies at both four weeks and six months were associated with the OR rate of patients. What is the impact? Our study suggests that ITP patients with anti-GPIb/IX positive autoantibodies respond poorly to DXM-RTX therapy. Platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX therapy in ITP patients. [ABSTRACT FROM AUTHOR]

The emergence of rituximab biosimilars offers the prospect of significant savings to the healthcare system. However, these drugs have never been evaluated for treating immune thrombocytopenia (ITP). This was an observational, matched study. We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from the historic ITP-ritux registry. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product. Response status was defined according to international criteria. We included 107 patients; 55 receiving Rixathon™ and 52 Truxima™. Three months after the first infusion of rituximab biosimilars, the overall response rate was 47/74 (63.5%) versus 76/142 (53.5%) for the matched controls receiving the reference product (p =.13). The 3-month overall response rate was 76.5% for Rixathon™ versus 51.5% for the matched control group (p =.01) and 21/40 (52.5%) for Truxima™ versus 41/74 (55.4%) for the matched controls (p =.81). For non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product. Rituximab biosimilars seemed safe and effective for ITP treatment. What is the context? Immune thrombocytopenia (ITP) is an autoimmune disease defined by a low platelet count without any other cause of thrombocytopenia. Patients with ITP may experience severe bleedings. Rituximab, a biotechnological therapy, is a valid second-line treatment option for ITP. Biotechnological therapies are expensive. Because the patent expiratory date of the reference product of Rituximab expired, highly similar drugs called biosimilars have been developed and used in ITP treatment without any direct evaluation in this particular disease. What is new? In this study, we evaluate the efficacy and safety of rituximab biosimilars versus the reference product for treating adult ITP We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from a historic registry that included ITP patients treated by the reference product. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product. For naïve and non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product. What is the impact? This study provides further evidence that rituximab biosimilars are safe and effective for immune thrombocytopenia treatment. [ABSTRACT FROM AUTHOR]

The association between T-cell large granular lymphocytes (T-LGL) and ITP is uncertain. The aims of this study were to determine the prevalence of T-LGL in patients with ITP and to describe its association with ITP disease severity. We analyzed flow cytometry results for T-LGL (using a threshold of 0.3 x109 or greater cells/L) or positive T-cell receptor clonality in patients with ITP and nonimmune thrombocytopenia. Descriptive statistics were used to characterize the association between T-LGL and ITP, response to ITP treatments (rituximab and splenectomy) and response to T-LGL treatment. Among ITP patients, 14.3% (13/91) had evidence of a T-LGL population compared to 10.3% (3/29) of patients with non-immune thrombocytopenia. ITP patients with T-LGL had lower nadir platelet counts (2 vs. 47 × 109/L) and received more ITP treatments (median 6 vs. 3) than ITP patients without T-LGL. Response to rituximab was observed in 14.3% (1/7) of ITP patients with T-LGL and 54.5% (6/11) without T-LGL. Response to splenectomy was observed in 25% (2/8) with T-LGL and 56.2% (9/16) without T-LGL. Four patients with ITP and T-LGL received treatment for T-LGL with methotrexate; none had an improvement in platelet count levels. T-LGL may appear in patients with ITP, and the meaning of this finding remains unclear; however, for some patients, the presence of abnormal T-LGL may indicate a more severe form of ITP that tends to be less responsive to therapy. In this cohort, treatment of T-LGL with methotrexate did not improve platelet counts in the few patients who were treated. [ABSTRACT FROM AUTHOR]

Primary effusion lymphoma (PEL), an aggressive non-Hodgkin lymphoma caused by Kaposi sarcoma-associated herpesvirus (KSHV), lacks standard therapy and has a median survival of 10–22 months with combination chemotherapy. PEL is a tumor of plasmablast-like B cells generally expressing CD38, the target of daratumumab (Dara). Initially, we assessed PEL cells from eight patients and established that each expressed high levels of CD38 by flow cytometry. PEL cell lines were also evaluated and most had high CD38 expression. We then assessed Dara's effects on complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) of PEL cell lines as well as its clinical benefits on two patients with PEL. Despite high CD38 expression, Dara did not induce CDC of PEL cell lines, due in part to high levels of the complement-inhibitory proteins, CD55 and CD59. However, Dara induced significant and dose-dependent increases in ADCC, particularly in those lines with high CD38 levels. Two FDA-approved drugs, all trans-retinoic acid (ATRA) and pomalidomide (Pom), significantly increased surface CD38 levels in low-CD38 expressing PEL cell lines, resulting in increased Dara-induced ADCC. Two patients with refractory PEL were treated with Dara alone or in combination with Pom. One patient with leptomeningeal PEL had a complete response to Dara and Pom combination treatment. Others had improvement in performance status and resolution of malignant ascites with Dara alone. Together, these data support the use of Dara monotherapy or in combination with ATRA or Pom as a potential therapeutic option for PEL. [ABSTRACT FROM AUTHOR]

Endogenous BFL1 expression renders diffuse large B-cell lymphoma (DLBCL) cells insensitive to B-cell lymphoma 2 (BCL2) and/or MCL1 inhibitors. Considering the difficulties in developing a direct BFL1 inhibitor, we intended to inhibit histone deacetylase (HDAC) to mitigate the biological role of BFL1 by modulating WT1 and NOXA. Cells expressing high BFL1 exhibited enhanced sensitivity to pan-HDAC inhibitor compared to low BFL1 expressing cells, mainly attributable to the difference in the amount of apoptosis. HDAC inhibitors decreased BFL1 and WT1 expressions while increasing NOXA levels. The BFL1 knockdown experiment demonstrated that HDAC inhibitor's sensitivity depends on the BFL1 expression in DLBCL cells. Furthermore, we found that the specific HDAC class was expected to play a critical role in BFL1 inhibition by comparing the effects of several HDAC inhibitors. Thus, our study provides a rationale for using HDAC inhibitors to induce apoptosis in DLBCL patients using BFL1 as a predictive biomarker. [ABSTRACT FROM AUTHOR]

Purpose: During neutrophil extracellular traps (NET) formation granulocytes release a decondensed chromatin web that is studded with antimicrobial proteins. These NET engulf and kill pathogens like bacteria and fungi. NET formation is part of the innate immune response but can also contribute to the aggravation of autoimmune diseases, thrombosis, and cancer metastasis. Anti-NET therapeutics to prevent potentially harmful consequences of excessive NET formation are warranted. Materials and methods: Therefore, we stimulated NET formation with ionomycin in the peripheral blood of 25 healthy individuals and quantified NET with flow cytometry and fluorescence microscopy after exposure to five different anti-inflammatory and cytostatic drugs. NET were identified by their expression of myeloperoxidase, citrullinated histone H3, and (extracellular) DNA release. Results: The preliminary in vitro drug screening indicated that acetylsalicylic acid (ASA) might suppress (−3.82%), and rituximab might enhance (+10.52%) NET formation. To consolidate the screening results, we quantified NET after exposure to rituximab and ASA in the blood of nine additional healthy subjects. Rituximab showed a significant increased NET formation compared to the neutrophils treated with ASA (a mean of differences 3.96%; 95% CI 1.90–6.03%; p <.01) or compared to neutrophils without treatment (a mean of differences 4.39%; 95% CI 1.17–7.61%; p =.01). Contrary to the screening results ASA showed no significant suppression of NET formation in the consolidation experiments (a mean of differences 0.43%; 95% CI −1.27 to 2.12%; p =.58). Conclusions: We conclude that rituximab therapy might further trigger activated NET formation and should be applied with caution in patients with pro-inflammatory state and underlying autoimmune disease, thrombosis, or cancer. [ABSTRACT FROM AUTHOR]

Indeed, CLL patients with a CD49d bimodal expression experience a clinical behavior similar to that of CD49d SP + sp CLL and show an overall increase of the CD49d SP + sp subpopulation under multiple lines of therapy, consistent with its selection in the microenvironmental niche. CD49d has emerged as one of the strongest negative prognosticators in chronic lymphocytic leukemia (CLL), marking a subset of ~40% of patients characterized by an aggressive and accelerated clinical course [[1]]. (B) CD49d modulation on D14 in CLL samples with or without stable CLLlow counts over time (i.e. CLL <0.1 × 103/ l for all time points of MRD analysis evaluated, CLLlown = 12, 8/12 CD49d+ samples vs. [Extracted from the article]

Safety of chemoimmunotherapy during pregnancy for treatment of Non-Hodgkin's lymphoma (NHL) is controversial. We review 37 cases of mothers with high grade NHL treated with rituximab and concurrent chemotherapy during pregnancy. Majority (95%) of mothers were treated in their second and third trimester, and a median of 4 cycles of combination therapy was administered. Complete remission occurred in 14/17 (82%) mothers whose disease outcomes were reported. There were 2 spontaneous abortions and 1 trimester fetal death that occurred in 3 mothers who received treatment in their first and second trimesters. Among the 34 (92%) live births, there were 6 cases of respiratory/cardiac complications requiring intervention and 5 cases of hematologic abnormalities reported. This review highlights the efficacy and safety of chemoimmunotherapy for mothers treated in second and third trimester. Further data is needed to establish recommendations for management of mothers with aggressive NHL in their first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Anti-glomerular basement membrane (anti-GBM) disease is a rare but severe autoantibody-mediated immune disorder. The typical clinical presentation includes rapidly progressive glomerulonephritis and often concurrent pulmonary hemorrhage. The present study is aimed to investigate the therapeutic effects of rituximab either used alone or with other immunosuppressants. Eight patients diagnosed with anti-GBM disease and treated with rituximab from 2014 to 2020 were retrospectively reviewed. Eight patients included 5 males and 3 females with a median age of 58.5 years. They all presented severe kidney injuries and 1 patient had lung hemorrhage. At diagnosis, the median of serum creatinine was 246 µmol/L (ranging from 91 to 850 µmol/L), with 3 patients requiring dialysis. All of them received corticosteroids and plasmapheresis. Rituximab was given as either standard four weekly doses or one pulse ranging from 100 to 600 mg. After a median follow-up of 34.5 months, kidney function was partially recovered or stabilized in 5/8 (62.5%) patients, free of dialysis. Anti-GBM antibodies remained undetected in all patients during follow-up. No severe adverse effect associated with rituximab was observed. Rituximab may be an alternative therapy in the treatment of patient with severe or refractory anti-GBM disease. [ABSTRACT FROM AUTHOR]

To retrospectively investigate the clinical characteristics, prognosis, treatment, and therapy outcome of Chinese patients with primary testicular lymphoma (PTL). we collected data of 49 PTL patients from four hospitals over 13 years. The median age was 63 years old. We described the clinical characteristics of the patients including the laterality, serum lactate dehydrogenase (LDH), pathology classification, stage, International prognostic index (IPI) scores and more. Complete remission (CR) was achieved in 34 patients and partial remission (PR) in 3 patients; Progressive disease (PD) was detected in 11 patients, and 10 patients died. The average progression-free survival (PFS) of all patients was 43.92 months, and the average overall survival (OS) was 47.55 months. The Ann Arbor stage, IPI score, and LDH were associated with OS, while Ann Arbor stage, IPI score, LDH, and histotype were significantly associated with PFS. Chemotherapy and radiotherapy following orchiectomy was associated with a significantly longer PFS. Most patients can achieve CR after induced therapy or orchiectomy. However, there are many associated prognostic factors. [ABSTRACT FROM AUTHOR]

To analyse the clinical characteristics and therapeutic response of Chinese patients with primary extranodal diffuse large B-cell lymphoma DLBCL (PE-DLBCL). We analysed the clinical features and outcomes of 197 patients who were newly diagnosed with PE-DLBCL between January 2015 and December 2020. The gastrointestinal tract showed the highest rate of involvement (34%), followed by the central nervous system (CNS) and intraocular system (31.5%). The 3-year overall survival (OS) rate was 81% for the entire group and 79% for those with CNS and vitreoretinal involvement. Ann Arbour stage, lactate dehydrogenase level, International Prognostic Index > 2, and complete remission (CR) were significantly related to the survival of patients with PE-DLBCL. The lack of CR was the only independent adverse prognostic factor for OS. The clinical outcomes of patients with PE-DLBCL at our centre were encouraging, especially for patients with CNS and vitreoretinal involvement. [ABSTRACT FROM AUTHOR]

Chemotherapy, including bendamustine, usually causes lymphocytopaenia and hypogammaglobulinaemia as side effects in patients with haematological malignancies. Therefore, the possibility has been considered that these immunological adverse events induced by bendamustine may lead to infectious diseases. However, lymphocytopaenia and/or hypogammaglobulinaemia have not yet been shown to have a statistically significant association with infection in cancer patients who receive bendamustine. We retrospectively studied 27 patients with relapsed or refractory indolent follicular lymphoma who were treated with bendamustine and rituximab (BR). In order to elucidate relationships between immune-related laboratory parameters (i.e. peripheral blood leukocyte, neutrophil, lymphocyte and immunoglobulin G [IgG]) and infectious events, receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed. Infectious diseases occurred in 11 patients (11/27, 41%), including 3 (3/27, 11%) with severe diseases. The area under the ROC curve (AUC) showed that the lowest IgG level during and after BR discriminated infectious events (cut-off value, 603 mg/dL) with 81.8% sensitivity and 68.8% specificity (AUC, 0.76; 95% CI, 0.52-0.90). Furthermore, a multivariate regression analysis revealed that the minimal serum IgG value during and after BR therapy was the only variable that was significantly associated with infection (odds ratio, 8.29; 95% CI, 1.19-57.62; p value, 0.03). Serum IgG ≤603 mg/dL during and after BR therapy was independently associated with an increased risk of infection. The monitoring of serum IgG during chemotherapy may help to predict the development of infection in blood cancer patients undergoing chemotherapy with bendamustine in combination with rituximab. [ABSTRACT FROM AUTHOR]