METHODS: In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity.
RESULTS: The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder.
CONCLUSION: Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate.
TRIAL REGISTRATION: NCT01892345 (ClinicalTrials.gov).
METHODS: Studies of adult patients with biopsy-proven SDNS/FRNS, administered any immunosuppressive agents and reported complete remission results as one of the clinical outcomes were included. Articles were independently screened by two researchers. ROBINS-I was used for risk of bias assessment. Random-effects model was used for statistical analysis and corresponding 95% confidence intervals (CIs) were calculated.
RESULTS: 574 patients across 28 studies were included in the analysis. Patients receiving rituximab have a complete remission rate of 89% (95% CI = 83% to 94%; τ2 = 0.0070; I2 = 62%; overall p < 0.01, low certainty) and adverse event rate of 0.26, cyclosporine (CR 40%; 95% CI = 21% to 59%; τ2 = 0.0205; I2 = 55%; overall p = 0.08, low certainty), tacrolimus (CR 84%; 95% CI = 70% to 98%; τ2 = 0.0060; I2 = 33%; overall p = 0.21, moderate certainty), mycophenolate mofetil (CR 82%; 95% CI = 74% to 90%; τ2 < 0.0001; I2 = 15%; overall p = 0.32, moderate certainty) and cyclophosphamide (CR 79%; 95% CI = 69% to 89%; τ2 = 0; I2 = 0%; overall p = 0.52, moderate certainty).
CONCLUSION: Among the commonly used immunosuppressive agents, only rituximab has a statistically significant effect in achieving complete remission among patients with SDNS/FRNS and has a relatively good safety profile, but this is limited by low quality of evidence with high degree of heterogeneity causing a lack of statistical power.
AIMS OF THE STUDY: To analyse pre-treatment clinical features of DLBCL patients that are predictive of R-CHOP therapy resistance and early disease relapse after R-CHOP therapy treatment.
METHODS USED TO CONDUCT THE STUDY: A total of 698 lymphoma patients were screened and 134 R-CHOP-treated DLBCL patients were included. The Lugano 2014 criteria was applied for assessment of treatment response. DLBCL patients were divided into R-CHOP resistance/early relapse group and R-CHOP sensitive/late relapse group.
RESULTS OF THE STUDY: 81 of 134 (60%) were R-CHOP sensitive/late relapse, while 53 (40%) were R-CHOP resistance/early relapse. The median follow-up period was 59 months ± standard error 3.6. Five-year overall survival rate of R-CHOP resistance/early relapse group was 2.1%, while it was 89% for RCHOP sensitive/late relapse group. Having more than one extranodal site of DLBCL disease is an independent risk factor for R-CHOP resistance/early relapse [odds ratio = 5.268 (1.888-14.702), P = .002]. The commonest extranodal sites were head and neck, gastrointestinal tract, respiratory system, vertebra and bones. Advanced age (>60 years), advanced disease stage (lll-lV), raised pre-treatment lactate dehydrogenase level, bone marrow involvement of DLBCL disease high Eastern Cooperative Oncology Group status (2-4) and high R-IPI score (3-5) showed no significant association with R-CHOP therapy resistance/early disease relapse (multivariate analysis: P > .05).
CONCLUSION AND CLINICAL IMPLICATIONS: DLBCL patients with more than one extranodal site are 5.268 times more likely to be R-CHOP therapy resistance or experience early disease relapse after R-CHOP therapy. Therefore, correlative studies are warranted in DLBCL patients with more than one extranodal site of disease to explore possible underlying mechanisms of chemoresistance.