Rituximab
Ontology highlight
ABSTRACT:
SUBMITTER: Tridente G
PROVIDER: S-EPMC7121599 | biostudies-literature | 2013 Jul
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The randomized phase 3 LYM3001 trial in relapsed follicular lymphoma (FL) demonstrated higher overall (ORR) and complete response (CR) rates and prolonged progression-free survival (PFS) with bortezomib-rituximab versus rituximab. We report findings in high-risk patients (FL International Prognostic Index [FLIPI] score ?3, and high tumor burden by modified Groupe d'Etude des Lymphomas Folliculaires [GELF] criteria).Patients aged ?18 years with grade 1/2 FL, ?1 measurable lesion, and documented relapse or progression following prior therapy, rituximab-naïve or rituximab-sensitive, were enrolled at 164 centers in 29 countries across Europe, the Americas, and Asia-Pacific. Patients were randomized (1:1) to five 5-week cycles of bortezomib-rituximab (bortezomib 1.6 mg/m2, days 1, 8, 15, and 22, all cycles; rituximab 375 mg/m2, days 1, 8, 15, and 22, cycle 1, and day 1, cycles 2-5; N=336) or rituximab alone (N=340). Randomization was stratified by FLIPI score, prior rituximab, time since last dose of anti-lymphoma therapy, and geographical region. The primary endpoint of the study was PFS.103 bortezomib-rituximab and 98 rituximab patients had high-risk FL. The ORR was 59% versus 37% (p=0.002), the CR/CRu rate was 13% versus 6% (p=0.145), and the durable response rate was 45% versus 26% (p=0.008) with bortezomib-rituximab versus rituximab. Median PFS was 9.5 versus 6.7 months (hazard ratio [HR] 0.667, p=0.012) with bortezomib-rituximab versus rituximab; median time to progression was 10.9 versus 6.8 months (HR 0.656, p=0.009); median time to next anti-lymphoma treatment was 14.8 versus 9.1 months (HR 0.762, p=0.103); and the 1-year Overall Survival rate was 83.1% versus 76.6%. Overall, 51% of bortezomib-rituximab and 32% of rituximab patients reported grade ?3 adverse events, including neutropenia (18%, 6%), anemia (4%, 5%), diarrhea (8%, 0%), thrombocytopenia (5%, 2%), and sensory neuropathy (1%, 0%).High-risk FL patients treated with bortezomib-rituximab had significantly higher ORR and longer PFS than patients receiving rituximab alone, with greater clinical benefit than in the overall study population; additional toxicity was acceptable and did not affect treatment feasibility.The phase 3 LYM3001 trial is registered with ClinicalTrials.gov, with the identifier NCT00312845.
| S-EPMC3502148 | biostudies-literature
Project description:Membranous Nephropathy (MN) is an autoimmune disease associated with antibodies against podocyte proteins: M-type phospholipase A2 receptor (PLA2R1) or thrombospondin type-1 domain-containing 7A (THSD7A) in 70 and 3% of patients, respectively. Antibody titer is correlated with disease activity: rising during active disease and decreasing before remission. Therefore, decreasing PLA2R1-Antibodies titer has become an important goal of therapy. Rituximab a chimeric monoclonal antibody induces remission in 60-80% of primary MN patients. All monoclonal antibodies such as rituximab can elicit antidrug antibodies, which may interfere with therapeutic response. We aim to analyze the relevance of anti-rituximab antibodies on the outcome of MN after a first course of rituximab. Forty-four MN patients were included and treated with two 1 g infusions of rituximab at 2-weeks interval. Anti-rituximab antibodies, CD19 count, and clinical response were analyzed. Then, we (i) analyzed the association of anti-rituximab antibodies at month-6 with response to treatment: remission, relapse and the need for another rituximab course; (ii) confirmed if anti-rituximab antibodies could neutralize rituximab B-cells depletion; and (iii) tested whether anti-rituximab antibodies could cross-inhibit new humanized anti-CD20 therapies. Anti-rituximab antibodies were detected in 10 patients (23%). Seventeen patients received a second rituximab course after a median time of 12 months (7-12), following nine cases of resistance and eight relapses. Anti-rituximab antibodies were significantly associated with faster B-cell reconstitution at month-6 (75 [57-89] vs. 2 [0-41] cells/μl, p = 0.006), higher proteinuria 12 months after rituximab infusion (1.7 [0.7; 5.8] vs. 0.6 [0.2; 3.4], p = 0.03) and before treatment modification (3.5 [1.6; 7.1] vs. 1.7 [0.2; 1.7] p = 0.0004). Remission rate 6 months after rituximab was not different according to anti-rituximab status (p > 0.99) but the rate of relapse was significantly higher for patients with anti-rituximab antibodies (p < 0.001). These patients required more frequently a second course of rituximab infusions (7/10 vs. 10/34, p = 0.03). Anti-rituximab antibodies neutralized rituximab activity in 8/10 patients and cross-reacted with other humanized monoclonal antibodies in only two patients. Three patients with anti-rituximab antibodies were successfully treated with ofatumumab. Anti-rituximab antibodies could neutralize rituximab B cells cytotoxicity and impact clinical outcome of MN patients. Humanized anti-CD20 seems to be a satisfying therapeutic alternative for patients with anti-rituximab antibodies and resistant or relapsing MN.
| S-EPMC6970431 | biostudies-literature
Project description:The addition of high-dose cytarabine to rituximab/bendamustine (RB) induction could improve outcomes for transplant-eligible patients with mantle cell lymphoma (MCL). We conducted a pooled analysis of 2 phase 2 trials and an off-trial cohort each testing 3 cycles of RB and 3 cycles of rituximab/high-dose cytarabine (RC) followed by autologous stem cell transplantation (ASCT) among untreated, transplant-eligible patients with MCL. Dana-Farber Cancer Institute (DFCI) and Washington University in St. Louis (WUSTL) led separate phase 2 trials testing sequential and alternating cycles of RB/RC, respectively. Patients treated at DFCI with sequential RB/RC off trial were retrospectively identified. Minimal residual disease (MRD) was assessed in the DFCI trial. A total of 88 patients (23 DFCI trial, 18 WUSTL trial, and 47 off trial) received RB/RC; 92% of patients completed induction, and 84% underwent planned consolidative ASCT. Grade 3 or 4 adverse events among trial patients included lymphopenia (88%), thrombocytopenia (85%), neutropenia (83%), and febrile neutropenia (15%). There were no treatment-related deaths during induction and 2 following ASCT. Among 87 response-evaluable patients, the end-of-induction overall and complete response rates were 97% and 90%, respectively. After a median follow-up of 33 months, 3-year progression-free survival and overall survival were 83% and 92%, respectively. Patients undergoing MRD testing experienced prolonged MRD negativity after ASCT with emergence of MRD occurring in only 1 patient who subsequently relapsed. RB/RC followed by ASCT achieves high rates of durable remissions in transplant-eligible patients with MCL. These trials were registered at www.clinicaltrials.gov as #NCT01661881 (DFCI trial) and #NCT02728531 (WUSTL trial).
| S-EPMC7065472 | biostudies-literature
Project description:Regulatory approval for a biosimilar product is provided on the basis of its comparability to an originator product. A thorough physicochemical and functional comparability exercise is a key element in demonstrating biosimilarity. Here we report the characterization of a proposed biosimilar rituximab (GP2013) and originator rituximab.To compare GP2013 with originator rituximab using an extensive array of routine analytical and extended characterization methods.Primary and higher order protein structures were analyzed using a variety of methods that included high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS), peptide mapping with UV and MS detection, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, hydrogen deuterium exchange (HDX) MS, 1D (1)H nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and differential scanning calorimetry (DSC). Charge and amino acid modifications were assessed using cation exchange chromatography (CEX) and peptide mapping using reversed-phase (RP) HPLC. Boronate affinity chromatography was used to determine the relative amount of glycation. Glycans were identified and quantified after 2-aminobenzamide (2-AB) labeling and separation using normal phase HPLC with fluorescence and MS detection, respectively. Glycan site occupancy was determined using reducing capillary electrophoresis with sodium dodecyl sulfate (CE-SDS). Size heterogeneity was determined using reducing and non-reducing CE-SDS, size exclusion chromatography (SEC) and asymmetric flow field flow fractionation (AF4). Biological characterization included a series of bioassays (in vitro target binding, antibody-dependent cell-mediated cytotoxicity [ADCC], complement-dependent cytotoxicity [CDC] and apoptosis) and surface plasmon resonance (SPR) Fc receptor binding assays.Intact mass analysis of GP2013 and the heavy and light chains using RP HPLC-ESI-MS revealed the expected molecular mass of rituximab. The amino acid sequence was shown to be identical between GP2013 and the originator rituximab. Further sequence confirmation using RP-HPLC-UV/MS peptide mapping showed non-distinguishable chromatograms for Lys-C digested GP2013 and originator rituximab. The higher order structure of GP2013 was shown to be indistinguishable from originator rituximab using a large panel of redundant and orthogonal methods. GP2013 and originator rituximab were comparable with regard to charge variants, specific amino acid modifications and the glycan pattern. GP2013 was also shown to have similar purity, aggregate and particle levels when compared with the originator. Functionally, and by using a comprehensive set of bioassays and binding assays covering a broad range of rituximab's functional activities, GP2013 could not be distinguished from originator rituximab.GP2013 was shown to be physicochemically highly similar to originator rituximab at the level of primary and higher order structure, post-translational modifications and size variants. An extensive functional characterization package indicated that GP2013 has the same biological properties as originator rituximab.
| S-EPMC3775154 | biostudies-literature
Project description:Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.
| S-EPMC6486816 | biostudies-literature
Project description:Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in most patients changed the management of MN dramatically, and provided a rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been investigated in several studies, including 3 randomized controlled trials, in which complete and partial remission of proteinuria was achieved in approximately two-thirds of treated patients. Due to its favorable safety profile, rituximab is now considered a first-line treatment option for MN, especially in patients at moderate and high risk of deterioration in kidney function. However, questions remain about how to best use rituximab, including the optimal dosing regimen, a potential need for maintenance therapy, and assessment of long-term safety and efficacy outcomes. In this review, we provide an overview of the current literature and discuss both strengths and limitations of "the new standard."
| S-EPMC8071613 | biostudies-literature
Project description:Several types of B-cell lymphoma have been successfully treated with rituximab, and approval by the US Food and Drug Administration for use of rituximab in the treatment of rheumatoid arthritis has increased interest in targeting CD20 on B cells for other indications. Although large amounts of rituximab can be infused into humans with no apparent dose-limiting toxicity, recent evidence suggests that the body's effector mechanisms, including complement-mediated cytotoxicity and natural killer (NK) cell-mediated killing, can be saturated or exhausted at high burdens of rituximab-opsonized B cells. One of the consequences of this saturation phenomenon is that the opsonized B cells are instead processed by a different pathway mediated by FcgammaR on effector cells. In this alternative pathway, both rituximab and CD20 are removed ("shaved") from the B cells and are taken up by monocytes/macrophages. This process, formerly called antigenic modulation, appears to occur in several compartments in the body and may play a key role in the development of resistance to rituximab therapy.
| S-EPMC2848181 | biostudies-other
Project description:This open-label phase 2 study (CONTRALTO) assessed the safety and efficacy of BCL-2 inhibitor venetoclax (VEN) plus rituximab (R), and VEN plus bendamustine (B) and R, vs B + R (BR) alone in relapsed/refractory (R/R) follicular lymphoma. Patients in the chemotherapy-free arm (arm A: VEN + R) received VEN 800 mg/d plus R 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 4, 6, 8, 10, and 12. After a safety run-in with VEN 600 mg, patients in the chemotherapy-containing cohort were randomized to either VEN + BR (arm B; VEN 800 mg/d for 1 year + 6 cycles of BR [B 90 mg/m2 on days 1 and 2 and R 375 mg/m2 on day 1]) or 6 cycles of BR (arm C). Overall, 163 patients were analyzed (9 in the safety run-in and 52, 51, and 51 in arms A, B, and C, respectively). Complete metabolic/complete response rates were 17% (arm A), 75% (arm B), and 69% (arm C). Of patients in arm B, only 61% received ?90% of the planned B dose vs 96% of patients in arm C. More frequent hematologic toxicity resulted in more reduced dosing/treatment discontinuation in arm B vs arm C. Rates of grade 3/4 adverse events were 51.9%, 93.9%, and 60.0% in arms A, B, and C, respectively. VEN + BR led to increased toxicity and lower dose intensity of BR than in arm C, but efficacy was similar. Optimizing dose and schedule to maintain BR dose intensity may improve efficacy and tolerability of VEN + BR, while VEN + R data warrant further study. This study was registered at www.clinicaltrials.gov as #NCT02187861.
| S-EPMC7735159 | biostudies-literature
Project description:BACKGROUND/AIMS:Real-world data about the treatment outcomes of patients receiving rituximab-containing immunochemotherapy followed by rituximab maintenance are required to understand better the treatment for follicular lymphoma (FL). METHODS:A cross-sectional study analyzed FL patients who were treated with R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and rituximab maintenance. RESULTS:Of 139 patients, 85 patients received R-CVP and 54 received R-CHOP. The characteristics did not differ significantly between the groups. Only grade 3 of FL was more common in R-CHOP. The complete response rate did not differ significantly between R-CHOP (50/54, 92.6%) and R-CVP (77/85, 90.6%). The number of disease relapses during rituximab maintenance did not differ significantly between the groups (p = 0.798). Therefore, the comparison of progression-free survival (PFS) showed no significant difference: the 3-year PFS rates for R-CVP and R-CHOP were 77% and 85%, respectively (p = 0.567). Although five of 56 hepatitis B virus (HBV) core antibody (anti-HBc)-positive patients experienced HBV reactivation, all cases of HBV reactivation were identified during regular monitoring for HBV DNA in blood, and were successfully managed with antiviral treatment. CONCLUSION:The survival outcomes of FL patients on rituximab maintenance after responding to R-CVP or R-CHOP were similar. Rituximab-containing immunochemotherapy followed by rituximab maintenance can be safely used for anti-HBc-positive patients if HBV DNA titer in blood can be regularly monitored.
| S-EPMC6960034 | biostudies-literature
Project description:Rituximab is a biologic agent that is usually well tolerated. With its increasing use for a myriad of rheumatologic and immunologic conditions, post-marketing surveillance has revealed more side effects. Systemic inflammatory response syndrome associated with cytokine release syndrome (CRS) is a very rare entity associated with the use of rituximab and carries a very high morbidity and case fatality rate. Cases of CRS reported within the literature are of patients with a very high tumor burden leading to a catastrophic cascade of events. We report the case of a patient having post-transplant lymphoproliferative disorder who died of fatal lactic acidosis and CRS within 24 h of receiving rituximab. Understanding the pathophysiology of such cases and identifying patients at risk may help to possibly avert this life-threatening complication.
| S-EPMC3364040 | biostudies-literature