Combination Of Rituximab Research Articles

Combination of rituximab and low-dose glucocorticoids for idiopathic refractory nephrotic syndrome with MCD/FSGS: a single-center prospective cohort study

Background The treatment of idiopathic refractory nephrotic syndrome (IRNS) remains a difficult problem in clinical practice. This study aims to determine the efficacy and safety of combining low-dose glucocorticoids with rituximab in IRNS treatment. Methods This prospective, single-center cohort study enrolled 60 patients who were diagnosed with refractory IRNS with minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) and treated at First Affiliated Hospital of Sun Yat-sen University. All patients received a treatment regimen consisting of rituximab (375 mg/m2/week × 4) and low-dose glucocorticoids. Results 46 complete remissions and 4 partial remissions were observed within 6 months of treatment. Within 12 months of treatment, 48 patients achieved complete remission, and 4 achieved partial remission. The complete remission rate for steroid-dependent/frequently relapsing nephrotic syndrome was significantly higher than that for steroid-resistant nephrotic syndrome (88.24% vs. 33.33%, p < .01). Following up for 12 months, 16 patients relapsed, accounting for 30.76% of the total, with a mean time to relapse of 10.97 months. Compared with baseline data, 24-hour urine protein quantification, total cholesterol and triglycerides significantly decreased, while serum albumin, globulin and IgG significantly increased at 12 months after treatment. All follow-ups were without serious adverse events. Twenty-four patients experienced infusion-related adverse reactions, which could be relieved by slowing down the infusion rate or suspending the infusion. Nine patients experienced infection-related adverse reactions; six of them were relieved with antibiotic treatment, and 3 patients were controlled by symptomatic treatment. Conclusions Rituximab combined low-dose glucocorticoids therapy is effective and safe in idiopathic refractory nephrotic syndrome.

Combination therapy of dexamethasone, rituximab, and cyclosporine for adults with primary immune thrombocytopenia: a prospective observational study

ABSTRACT Background To assess the effectiveness of the combination of dexamethasone, rituximab, and cyclosporine in treating adults with primary immune thrombocytopenia (ITP). Research design and methods This prospective study enrolled consecutive adult patients diagnosed with ITP at the 967th Hospital of the Chinese People’s Liberation Army Joint Service Support Force Hospital between November 2019 and February 2023. Results Twenty-eight patients (13 males, median age 43.5 years) were included. All patients previously experienced ineffective or relapsed ITP, with a median disease duration of 26.5 (range, 7-72) months. At baseline, the median platelet (PLT) count was 13.5 × 109/L (8.25-20 × 109/L). Following treatment, the PLT counts were significantly increased at weeks 1, 3, and 4. The early response rates at weeks 1 and 4 were 82.1% (23/28 patients) and 71.4% (20/28 patients), respectively. The 1-, 3-, and 6-month response rates were 71.4% (20/28), 67.9% (19/28), and 75% (21/28). The treatment-free survival rates at 12 and 24 months were 82.35% (14/17) and 71.43% (10/14), respectively. Six patients experienced transient adverse reactions. Conclusions The combination of dexamethasone, rituximab, and cyclosporine may present a promising therapeutic option for patients with refractory ITP, with good tolerability and mild adverse reactions.

Treatment of retroperitoneal fibrosis with rituximab, cyclophosphamide and dexamethasone, followed by rituximab and dexamethasone maintenance, achieved disappearance of pathological PET accumulation of FDG and regression of fibrotic masses after 4 months….

Idiopathic retroperitoneal fibrosis is characterized by the development of inflammatory infiltrates with marked fibrosis along the large retroperitoneal vessels. Rituximab in combination with glucocorticoids constitute an effective therapy, but the responses are not long-lasting. In other similar situations, addition of cyclophosphamide to the combination achieved longer and deeper responses. This was the reason to use the triple combination in this case. A 56-year-old man came with four weeks lasting abdominal pain with CT finding of retroperitoneal fibrosis with unilateral ureteral occlusion. Biopsy confirmed retroperitoneal fibrosis with histological findings of IgG4-associated disease. Treatment with prednizone was poorly tolerated. Therefore, the patient was switched to the combination of rituximab 375 mg/m2 on day 1, cyclophosphamide 300 mg/m2 in infusion in days 1 and 15, plus dexamethasone 20 mg in infusion on days 1 and 15, repeated in a 28-day cycle. Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) examination after 4 months of treatment showed a marked decrease in FDG accumulation and complete disappearance of the fibrotic mass. After 8 months, the induction therapy was followed by maintenance therapy with rituximab 1,000 mg plus dexamethasone 20 mg in 6-month intervals. Control PET/MR examination after 3 years is consistent with complete remission. The number of circulating plasmablasts correlated with the disease activity. Treatment of retroperitoneal fibrosis with the tripple combination of rituximab, cyclophosphamide and dexamethasone achieved a very rapid disappearance of pathological FDG accumulation and fibrotic retroperitoneal mass, with complete disappearance achieved after 4 months of treatment. After 3 years of maitenance therapy, the diesease is still in complete remission on PET/MR examination. We suggest to continue the maintenance therapy with rituximab because of some increase in the number of circulating plasmablasts after prolongation of the intervals between rituximab administration.

Real-World Efficacy and Safety of the Combination of Rituximab, Lenalidomide, and Ibrutinib in Patients with Relapsed and/or Refractory Non-Hodgkin Lymphoma

Real-World Efficacy and Safety of the Combination of Rituximab, Lenalidomide, and Ibrutinib in Patients with Relapsed and/or Refractory Non-Hodgkin Lymphoma

Effective management of necrotizing crescentic glomerulonephritis using an aggressive combination therapy including avacopan in a patient double-seropositive for anti-GBM antibodies and ANCA: a case report.

The prognosis of anti-glomerular basement membrane (anti-GBM) nephritis, often accompanied by the presence of antineutrophil cytoplasmic antibodies (ANCA), is poor, and even with aggressive therapeutic approaches, kidney replacement therapy (KRT) is typically required. Here, we present a case of necrotizing crescentic glomerulonephritis in a patient double-seropositive for anti-GBM antibodies and ANCA who successfully achieved dialysis independence following aggressive treatment, including avacopan. The patient was a 77-year-old woman with rapidly progressive glomerulonephritis and double seropositivity for myeloperoxidase-ANCA and anti-GBM antibodies. A kidney biopsy revealed diffuse cellular crescents with necrosis and immunoglobin (Ig)G1 and IgG3 positivity on immunofluorescence staining, leading to a histological diagnosis of anti-glomerular basement membrane nephritis. Our treatment approach involved a novel combination of glucocorticoids, rituximab, low-dose cyclophosphamide, and plasma exchange complemented by avacopan. Temporary hemodialysis was required, and the patient successfully discontinued dialysis after 12 sessions despite a poor histological prognosis. This case underscores the significance of considering aggressive therapeutic strategies, including avacopan, for severe anti-GBM nephritis, even in the absence of lung involvement, to avert the need for KRT.

Mycophenolate Mofetil for the Treatment of Warm Autoimmune Haemolytic Anaemia Post-Rituximab Therapy: A Case Series.

Warm autoimmune haemolytic anaemia (wAIHA) is an acquired haemolytic disorder most commonly treated with a combination of corticosteroids, rituximab and/or splenectomy. Third-line therapies for refractory cases include immunosuppressive agents. Mycophenolate mofetil is frequently used in these scenarios, although its use is supported by small studies and anecdotal evidence rather than large-scale data. We describe three cases of refractory warm autoimmune haemolytic anaemia successfully treated with mycophenolate mofetil. Case 1: A persistent case of autoimmune haemolytic anaemia in a 56-year-old was ultimately managed with mycophenolate mofetil, leading to successful steroid tapering and stable haemoglobin levels without relapse. Case 2: A woman with a complex oncological history, including lymphoma and breast cancer, achieved remission with mycophenolate therapy, maintaining stability post-steroid treatment. Case 3: Mycophenolate proved effective for a 63-year-old with cirrhosis after recurrent autoimmune anaemia and deep vein thrombosis, enabling cessation of steroids and maintaining remission. Management of this condition can be challenging and balancing the available treatments is crucial to reduce potential complications from long-term therapies that appear to be ineffective. Our case series demonstrates anecdotal experience on successful use of mycophenolate mofetil for complex refractory cases of wAIHA. Warm autoimmune haemolytic anaemia can be a challenging condition to manage. Refractory cases that are steroid-dependent can benefit from trialling steroid-sparing agents such as mycophenolate.Anti-CD20 agents such as rituximab can be very effective in refractory cases, however there is a small percentage of patients that might not be responsive to this monoclonal antibody.Autoimmune haemolytic anaemias can be frequently complicated by thrombotic events, and part of the backbone treatment is establishing good thromboprophylaxis.

Combination of rituximab and methotrexate followed by rituximab and cytarabine in elderly patients with primary central nervous system lymphoma.

The optimal treatment strategy for newly diagnosed primary central nervous system lymphoma (PCNSL) has yet to be established, especially in the elderly. In the current study, we conducted a phase II study to evaluate the efficacy and safety of rituximab plus high-dose MTX followed by rituximab plus cytarabine in patients aged ≥60 years newly diagnosed with PCNSL. Patients received an induction treatment of high-dose methotrexate plus rituximab followed by two cycles of a consolidation treatment of cytarabine plus rituximab. The primary end-point was a 2-year progression-free survival (PFS) rate. A total of 35 patients were recruited, and their median age was 73 (range: 60-81). After induction treatment, the complete and partial responses (PRs) were 56% and 20% respectively. Twenty-six patients proceeded to the consolidation treatment; the complete and PRs were 59% and 9% respectively. After a median follow-up duration of 36.0 months, the 2-year PFS rate was 58.7%. Treatment was generally well-tolerated as only three patients were withdrawn from the study due to toxicity, and no treatment-related mortality was reported. The 2-year overall survival rate was 77.9%. The current study may suggest the feasibility of administering high-dose MTX plus cytarabine in PCNSL patients aged ≥60 years and the potential role of additive rituximab.

Daratumumab for De-sensitization of Donor Specific Antibodies: Is it a Quicker and Easier way?

Antibodies directed against donor-specific HLA loci (DSA) has been proved as a main culprit for graft rejection, more specifically in HLA mismatched and haplo-identical transplant settings. There is no standardized regimen to manage the presence of DSAs in allogeneic stem cell transplantations (allo-SCTs). Most widely regimen includes combination of rituximab (anti CD20 antibody), Immunoglobulin (IVIG), plasma exchange, and buffy coat infusion, which is costly and time-consuming. Daratumumab (anti CD38 monoclonal antibody) is an effective therapeutic agent to deplete plasma cells and hence, it has a potential to reduce DSA. It has been utilized widely in solid organ transplantation for this purpose. We used this agent in two haplo-identical transplant patients to eliminate or reduce DSA. We observed definite either reduction or elimination in DSA levels in these cases and we could perform haplo-identical transplantation without much delay and with successful primary engraftment in both scenarios. We emphasize that literature on real-world utilization of daratumumab in allo-SCTs is limited. However, it has been utilized widely in solid organ transplantation for this purpose. Our experience with daratumumab regarding effective reduction of DSA followed by successful engraftment might encourage its use in de-sensitization protocols without much delay in transplantation.

Waldenström Macroglobulinemia - A State-of-the-Art Review: Part 1: Epidemiology, Pathogenesis, Clinicopathologic Characteristics, Differential Diagnosis, Risk Stratification, and Clinical Problems.

Waldenström macroglobulinemia (WM) is an infrequent variant of lymphoma, classified as a B-cell malignancy identified by the presence of IgM paraprotein, infiltration of clonal, small lymphoplasmacytic B cells in the bone marrow, and the MYD88 L265P mutation, which is observed in over 90% of cases. The direct invasion of the malignant cells into tissues like lymph nodes and spleen, along with the immune response related to IgM, can also lead to various health complications, such as cytopenias, hyperviscosity, peripheral neuropathy, amyloidosis, and Bing-Neel syndrome. Chemoimmunotherapy has historically been considered the preferred treatment for WM, wherein the combination of rituximab and nucleoside analogs, alkylating drugs, or proteasome inhibitors has exhibited notable efficacy in inhibiting tumor growth. Recent studies have provided evidence that Bruton Tyrosine Kinase inhibitors (BTKI), either used independently or in conjunction with other drugs, have been shown to be effective and safe in the treatment of WM. The disease is considered to be non-curable, with a median life expectancy of 10 to 12 years.

A novel approach to induce early remission in high-risk primary membranous nephropathy.

This prospective single-arm trial with historic controls evaluated the efficacy and safety of treatment based on a combination of rituximab, intravenous cyclophosphamide, and corticosteroids (RCP) administered at lower cumulative doses for the induction of early remission in primary membranous nephropathy (PMN). We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n=15) or cyclosporine+corticosteroids (CSA, n=42). The primary outcomes were complete remission (CR) and overall remission (OR) by month 12 and the time to remission. In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P≤0.009) and the CSA group (50% and 24%, P≤0.003). The median time to OR (2.8 (1.6-3.9) months) was shorter compared to RTX (7.1 (3.4-17.5) months, P=0.008) and CSA (7.3 (6.0-13.6) months, P<0.001). In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI: 2.8-9.6) and 4.8 (95% CI: 2.2-10.3), respectively. Propensity score-matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years. RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.

Phase I safety and preliminary efficacy of IMM0306 in combination with lenalidomide in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma.

e19040 Background: The combination of rituximab (anti-CD20 mAb) and lenalidomide was approved for use in relapsed or refractory (R/R) indolent non-Hodgkin's lymphoma (iNHL). IMM0306 is a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα on both heavy chains. It exerts excellent cancer killing efficacy by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcɣR engagement. Here, we report on a Phase I study of 8 patients (pts) with R/R CD20-positive B-cell NHL. Methods: This is an open-label, multicenter phase I study (NCT05771883). The study is designed to use "3+3" scheme for dose escalation exploring in 2 dose levels of IMM0306 (1.6 mg/kg, 2.0 mg/kg), intravenously administered each week in each 28-day cycle; while lenalidomide will be administered as fixed dose of 20 mg for NHL, taken orally once daily for the first 21 days of each 28-day cycle to determinate maximum tolerated dose (MTD). Dose-limiting toxicity (DLT) was evaluated in the first 28 days of the combination therapy. Safety was evaluated per CTCAE 5.0, tumor assessments performed once every 8 weeks by Lugano 2014. Results: As of Jan 5, 2024, 8 pts with R/R follicular lymphoma (FL, n=6) and marginal zone lymphoma (MZL, n=2) were enrolled. The median age was 52.5 years with 7 (87.5%) males. The median prior line of therapy was 1. All pts received previous anti-CD20 therapy. Among 7 efficacy evaluable pts, 1 CR (FL), 4 PR (2 FL, 2 MZL), and 1 SD were seen. The ORR and DCR were 71.4% and 85.7%, respectively. Two DLTs (grade 4 PLT decreased without bleeding) were observed at 2.0 mg/kg IMM0306 + 20 mg Lenalidomide dose level, but none at the dose level of 1.6 mg/kg IMM0306 + 20 mg Lenalidomide. The most common treatment related adverse events (TRAEs) were lymphocyte decreased (62.5%), ANC decreased (62.5%), WBC decreased (50%), anemia (50%), bilirubin increased (50%), PLT decreased (37.5%), infusion-related reactions (37.5%). Grade ≥3 TRAEs occurred in 6 pts, including lymphocyte decreased (62.5%), PLT decreased (25%), WBC decreased (12.5%), ANC decreased (12.5%) and pneumonia (12.5%). One pt experienced treatment related serious adverse event. 5 patients experienced TRAEs, leading to the study drug interruption, while no patients experienced TRAEs leading to the study drug discontinuation or death. 2 pts had a dose reduction of IMM0306 (2.0 mg/kg dose level), 3 pts had dose reductions of lenalidomide due to TRAEs. Pharmacodynamics analysis demonstrated IMM0306 combine lenalidomide effectively depleted B cell in peripheral blood within 24 hours. Conclusions: 1.6 mg/kg IMM0306 in combination with 20 mg lenalidomide was well-tolerated and with a robust preliminary anti-tumor activity in pts with R/R FL and MZL. The phase I study is ongoing. Clinical trial information: NCT05771883 .

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

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

#2748 Combined rituximab and daratumumab treatment in difficult to treat nephrotic syndrome cases

Abstract Background and Aims Common treatments for multidrug-resistant and multidrug-dependent nephrotic syndrome (NS) are inconsistently effective and burdened by long-term toxicities. Moreover, affected patients are at high risk of progression to end-stage kidney failure. Objective To test the safety/efficacy profile of combined single infusion of rituximab and daratumumab in inducing proteinuria remission in multidrug resistant nephrotic syndrome and maintaining drug free disease remission in patients with multidrug-dependent nephrotic syndrome after removal of oral immunosuppression. Method We here present a Phase 2 Proof-of-Concept single-arm clinical trial, that enrolled consecutive participants at the Nephrology Unit of the IRCCS Giannina Gaslini Children's Hospital in Genoa, Italy, between September 2021 and March 2023. Enrolled patients, aged between 3 and 24 years, were multidrug-dependent or multidrug-resistant nephrotic syndrome for at least 12 months before enrolment. Multidrug-dependency was defined by the need of at least 2 oral immunosuppressive drugs (prednisone and/or calcineurin inhibitors and/or mycophenolate mofetil) and by the occurrence of at least two consecutive relapses on two immunosuppressive drugs. Multidrug-resistance nephrotic syndrome was defined by the lack of antiproteinuric effect of a double immunosuppressive therapy. Exclusion criteria included genetic forms of NS and administration of monoclonal therapies in the last 9 months before enrolment. Interventions: Rituximab and daratumumab were administered as single doses at 375 mg/m2 and 16 mg/kg, respectively, 15 days apart. Main Outcomes and Measures:Proteinuria, serum albumin, Immunoglobulin M and G, B and T lymphocyte subsets, safety, Quality of Life. Results A total of 7 consecutive multidrug-resistant and 16 multidrug-dependent NS, respectively, were enrolled. In multidrug-resistant NS, combined rituximab and daratumumab promoted complete or partial remission in 6 patients (Fig. 1A). Five subjects experienced proteinuria relapse, that was effectively treated with a second course of combined treatment. Decreased of I'm, but not IgG, correlated with improvement of proteinuria (Fig. 1B).These treatment allowed to reduce the chronic immunosuppressive treatment daily administered (Fig. 1C). In multidrug-dependent NS, combined rituximab and daratumumab extended the relapse-free time, allowing us to remove oral immunosuppressant (Fig. 1D). Disease relapse was invariably anticipated by a recovery of circulating IgM:patients with IgM levels below median values measured at 3 mo post-treatment had a significantly lower rate of relapse at 9 mo than patients with higher IgM levels at 3 mo (Fig. 1E). Combined treatment induced significative reduction of CD38+ plasma cells (Fig. 1F) and IgM, but not IgG. Treatment was well tolerated and significantly increased quality of life. Conclusion Combined rituximab and daratumumab was safe and effective in the treatment of complicated forms of NS, offering a new therapeutic option for this severe condition.

#777 Renal recovery for patients with ANCA-associated vasculitis and low eGFR in a Spanish cohort

Abstract Background and Aims Renal failure secondary to ANCA-associated vasculitis (AAV) represents a clinical and therapeutic challenge [1]. Fifteen percent to 38% of the patients develop end-stage kidney disease within 5 years, and once patients need dialysis, 29% to 82% die or remain on dialysis 3 to 6 months after its initiation [2]. Therefore, effectively managing renal vasculitis and preventing patients from reaching dialysis have important consequences [2]. A post hoc analysis of ADVOCATE trial examined outcomes in a patient subgroup with severe renal insufficiency (i.e., estimated glomerular filtration rate (eGFR) ≤20 ml/min per 1.73 m2) at enrollment into the trial, and observed an average eGFR increase of 16.1 and 7.7 ml/min per 1.73 m2 in the avacopan and prednisone groups, respectively (P = 0,003) [2]. This study aimed to compare the average eGFR increase in our cohort of AAV with severely reduced GFR (&amp;lt;20 ml/min) treated with different induction treatment schemes. Method We performed a retrospective study which included 19 patients with the diagnosis of AAV and severe renal insufficiency at onset with eGFR between 15 to 20 ml/min per 1.73 m2. We analyzed the eGFR increase after 12 months of follow-up, according to the induction treatment scheme: cyclophosphamide, rituximab, a combination of cyclophosphamide and rituximab and other (prednisone alone, prednisone with plasma exchange or prednisone with mycophenolic acid). We compared our results to those obtained in the avacopan and prednisone groups in the ADVOCATE trial. Results In the subgroup of eGFR between 15 to 30 ml/min per 1.73 m2, patients had at enrollment a mean eGFR of 21 ± 5 ml/min per 1.73 m2 and after 12 months of follow-up the mean eGFR was 41 ± 23 ml/min per 1.73 m2 with an increase of 20 ± 23 ml/min per 1.73 m2. In the subgroup of eGFR between 15 to 20 ml/min per 1.73 m2, patients had at enrollment a mean eGFR of 17 ± 2 ml/min per 1.73 m2 and after 12 months of follow-up, the mean eGFR was 35 ± 20 ml/min per 1.73 m2 with an increase of 18 ± 21 ml/min per 1.73 m2. After 12 months of follow-up, the mean increase of eGFR was 18, 17, 10 and 23 ml/min per 1.73 m2 in the cyclophosphamide, rituximab, a combination of cyclophosphamide and rituximab and other groups, respectively. We compared our results with the post hoc analysis of the ADVOCATE trial in Table 1 and our results are similar to the avacopan group and better than the prednisone group (p &amp;lt; 0.05). Conclusion In our cohort of eGFR between 15 to 20 ml/min per 1.73 m2 at enrollment, the mean increase in eGFR after 12 months of follow-up was similar to the avacopan group and greater than the prednisone group in the ADVOCATE trial.

#3105 Tocilizumab for treatment of antibody mediated rejection in kidney transplant patients

Abstract Background and Aims Chronic active antibody-mediated rejection (caABMR) causes 40% of long-term graft failure after kidney transplantation (KT). Early treatment is of great importance, however, hard clinical evidence is still lacking. Currently the combination of plasmapheresis (PF), rituximab and intravenous immunoglobulin is used as standard treatment. Tocilizumab (TCZ) is a monoclonal antibody, IL-6 receptor antagonist, and it inhibits the production of donor-specific antibodies (DSA). We hypothesized that tocilizumab administration has an additional effect on graft survival and non-inferior to standard therapy in KT patients with ABMR. Method Retrospective single-center noninferiority case-control study was performed by involving 73 KT patients (43.5 ± 14.3 years, females 31, eGFR 19.5 ± 13.4) with biopsy proven ABMR diagnosed between June 2017 and May 2022. 19 patients received 8 mg/kg intravenous TCZ therapy for 6 months (12 aABMR, 7 caABMR, 38.6 ± 12.8 years, females 6). In the control group (C, n=54, 10 aABMR, 44 caABMR, 45.2 ± 14.5 years, females 25), 20 patients received plasmapheresis treatment, the rest stayed on optimized maintenance therapy (tacrolimus, mycophenolic acid, prednisolone). Baseline demographic data, standard laboratory data, proteinuria and DSA level were also monitored and analyzed. Results Graft loss occurred in 13 cases (6 aABMR, 7 caABMR) in KT on TCZ therapy and 43 (6 aABMR, 37 caABMR) in C group, meaning significantly lower risk of graft loss in the TCZ group (RR 0.69, p=0.036) during the median follow-up of 11.3 (IQR 2.5-23.1) months. In TCZ group, all caABMR patients lost their graft during the observation. In TCZ group, 1 year after the TCZ treatment, DSA (pooled) was lower (7028 (575-17782) versus 1605 (551-16903), p&amp;lt;0.05). Conclusion Early administration of TCZ seems to be noninferior to standard therapy and effective to prevent early graft loss as part of standard therapy in aABMR. Further clinical studies are needed to clarify clinical indications of TCZ and its long-term effects on the course of chronic active ABMR.

Long-term results of the sequential combination of cladribine and rituximab in Hairy cell leukemia

We 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.

Understanding the intrinsic biology of diffuse large B-cell lymphoma: recent advances and future prospects.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoid tumor, and accounts for approximately 30-40% of non-Hodgkin lymphomas. Although the prognosis has significantly improved with the advent of rituximab combination chemotherapy in the early 2000s, recurrence still occurs in about 40% of cases. Even though chemotherapy with increased dose-intensity is used in recurrent cases, the prognosis of such patients remains poor. Thus, the development of personalized medicine, including molecular-targeted drugs, is required to improve the prognosis of DLBCL patients, and further understanding of the molecular pathogenesis of DLBCL is essential for this purpose. With recent advances in genetic analysis technology, unknown genetic abnormalities and gene expression patterns have been discovered, and based on these discoveries, progress is being made in elucidating and subdividing molecular pathologies. This article summarizes recent findings regarding molecular pathogenesis in DLBCL using transcriptome and genomics technologies, and outlines the path to personalized medicine.

Abstract CT145: The final results of a phase I study using velcade (bortezomib), cladribine, and rituximab (VCR) in treating elderly patient with mantle cell lymphoma

Abstract Background: Mantle cell lymphoma (MCL) is a moderately aggressive and incurable small to medium size B cell lymphoma. In this phase 1 study, we evaluated the safety and efficiency of Valcade, Cladribine, and Rituximab (VCR) combination treatment in MCL. Patients and Methods: This is a single arm, open label, investigator-initiated Phase 1 study. This study employed a standard 3+3 dose escalation scheme designed to determine the maximum tolerated dose (MTD) of Cladribine in VCR regimen. The treatment scheme and Cladribine dose escalation levels (1, 2, and 3) are as follows: the therapy consisted of 6 28-day cycles. At first cycle of the treatment, Rituximab 375 mg/m2 infusion started on day 5 of the first week and then given weekly for 3 weeks; in the next 5 cycles, Rituximab was given on day 5 of each cycle, and then every 2 months as the maintenance therapy. Cladribine 35 mg/m2 (3 mg/m2 for level 1, 4 mg/m2 for level 2, and 5 mg/m2 for level 3) infusion was given on days 1 to 5 for 6 cycles. If the patient was older than 70 years old, Cladribine was only given on days 1 to 3 of each cycle. Velcade 1.6 mg/m2 subcutaneous injection was given on days 12, 19 and 26 for cycles 1 to 3, then Day 5 and 19 during Cycles 4 to 6, then once per month as maintenance therapy until toxicity or progression of the disease. The primary endpoint of this study was to investigate the dose limiting toxicity (DLT), safety, and efficiency of this regimen in patients with MCL. The secondary endpoints included remission rate (RR), progression free survival (PFS) and overall survival (OS). This study is registered with clinicaltrials.gov (NCT01439750). Results: No subject experienced dose limited toxicity (DLT) at either level 1 or 2, one possible DLT (infectious colitis) was observed on a subject during 2nd cycle at level 3. Then no additional DLTs were seen in 3 subjects added to level 3. Overall, this study recruited 13 subjects, with a median age of 64 years old (range from 55 to 83), and a total of 11 male and 2 females. Ten subjects were never previously treated, while 3 either relapsed or failed previous treatments. The majority of subjects tolerated this regimen well. Two relapsed patients experienced disease progression after received two cycles of treatments and died in 5 and 7 months after initiating the treatment. Another patient died 15 months after starting treatment. The overall remission (OR) rate was 77% (10/13) and complete remission (CR) rate was 85% (10/13). In newly diagnosed subject cohort, the RR and OS rates were 90% (9/10), PFR was 80% (8/10), and CR rate was 100% (10/10), of which 3 patients have been followed for more than 4 years, 3 other patients for more than 3 years, and 3 others for over 2 years. However, in relapsed/refractory subject cohort, 1 subject achieved CR for 7 months but then relapsed, 2 subjects had no response. There were 2 blastoid subjects, one was newly diagnosed and achieved CR.No severe systemic toxicity was observed in this study. Bone marrow suppression caused prolonged anemia and thrombocytopenia were the most common toxicity (3/13 with ≤grade 2). Low grade peripheral neuropathies (≤grade 2) were observed in 15% (2/13). Mild fatigue was a frequent complaint. Conclusions: The VCR combination is a well-tolerated, low toxicity and effective regimen for for untreated MCL. Cladribine 5 mg/m2 is a tolerable dose with manageable toxicity. Citation Format: Jeffrey J. Pu, Kristin Berger, David Claxton, Joseph Drabick, Thomas Loughran, Elliot Epner. The final results of a phase I study using velcade (bortezomib), cladribine, and rituximab (VCR) in treating elderly patient with mantle cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT145.

Efficacy and safety of lenalidomide in the treatment of B-cell non-Hodgkin lymphoma

BackgroundThe combination of rituximab and chemotherapy is a first-line treatment for patients with B-cell non-Hodgkin lymphoma. Lenalidomide is an immunomodulatory drug that has shown promising properties and activity in a variety of hematological malignancies. This study evaluated the efficacy and safety of lenalidomide-based regimens in the treatment of B-cell non-Hodgkin lymphoma.MethodsThe PubMed, Science Direct, ClinicalTrials.gov, and Web of Science databases were searched for relevant studies published up to May 2022. Studies with patients diagnosed with non-Hodgkin B-cell lymphoma, who were randomly assigned to a lenalidomide treatment group or a non-lenalidomide control group were considered for inclusion in this review and meta-analysis. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of the time-to-event outcomes and risk ratios (RRs) with 95% CIs of dichotomous data were estimated.ResultsA total of 3593 patients from 10 studies were evaluated. The results of the pooled analysis indicated that the lenalidomide-based regimen was associated with prolonged overall survival (HR, 0.85; 95% CI 0.74–0.97; P = 0.02) and progression-free survival (HR, 0.70; 95% CI 0.57–0.88; P = 0.002). Significant differences were found in the overall response rate (RR, 1.18; 95% CI 1.04–1.33; P = 0.01) and complete response rate (RR, 1.18; 95% CI 1.00–1.39; P = 0.05) between the treatment and control groups.ConclusionsLenalidomide appears to be a promising therapeutic agent that offers the possibility of a novel combination of chemotherapy free regimen for patients with B-cell non-Hodgkin lymphoma.

Effectiveness and safety of mycophenolate mofetil and rituximab combination therapy for immune idiopathic myopathies

IntroductionIdiopathic inflammatory myopathies (IIM) represent a rare and heterogenous group diseases, and their treatment is not fully defined yet. According to previous small case series, the combination of mycophenolate mofetil (MMF) and rituximab (RTX) may be effective in controlling difficult-to-treat patients. Our aim was to further explore the efficacy and safety of this combined approach in patients with IIM.MethodsPatients with IIM treated with the RTX/MMF combination in our Center were retrospectively identified. After the start of combination therapy, the efficacy was evaluated at 12 months (T12) according the 2016 ACR/EULAR response criteria for IIM. Cardiac imaging and pulmonary function tests were used to monitor disease activity in patients with myocarditis and interstitial lung disease, respectively. Adverse events were recorded over the follow-up period.ResultsAmong the 20 patients (median age 61 years; 70% female) included in the study, anti-synthetase syndrome was the most prevalent IIM subgroup (60%). At treatment start, muscle, heart, and lung were the most commonly actively affected organs. After 12 months, a moderate or major response was observed in all patients, and creatine kinase was significantly decreased (p-value = 0.012). Cardiac imaging and enzymes monitoring showed a reduction of heart inflammation, while pulmonary function tests improved in patients with lung involvement. No severe side effects were observed.ConclusionOur data show that combination of RTX and MMF is effective and safe in patients with severe and refractory IIM. Therefore, this combined treatment might represent a feasible approach for difficult-to-treat IIM cases.