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We conducted a systematic review of grade 3/4 adverse events (AEs) reported in prospective trials enrolling patients with follicular lymphoma (FL) and mantle cell lymphoma (MCL) receiving maintenance rituximab (MR). Random-effects models were used to calculate summary estimates and 95% confidence intervals for the proportion of AEs occurring during MR. Differences by induction program, histology, setting and MR schedule were examined by stratified analyses and univariate random-effects meta-regression. Eleven trials met the search criteria, with nine sufficiently reporting AEs during the MR phase. Of 1009 patients receiving MR, the proportion experiencing cumulative grade 3/4 toxicity was 24% (95% confidence interval [CI]: 14-36%). Patients receiving MR every 6 months as four weekly infusions for 2 years had significantly less toxicity compared with those receiving MR every 2 months (10% vs. 28%; p = 0.035). Patients treated with rituximab alone during induction had fewer toxicities compared to those treated with rituximab plus chemotherapy induction (12% vs. 35%; p = 0.031). Myelosuppression and infections were the most common toxicities. Our literature analysis suggests that MR given every 6 months and rituximab alone as induction may be associated with fewer grade 3/4 AEs for patients with FL and MCL; however, assessing the true independent impact of induction regimens and schedule on toxicity will require prospective trials. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) shares immunophenotypic and karyotypic features with chronic lymphocytic leukaemia. The latter comprises two distinct entities with prognosis dependent upon immunoglobulin heavy chain (IgH) gene mutational status and the presence of 11q deletion. We evaluated the relevance of IgH gene mutational status, IgV gene family usage and presence of 11q deletion in a series of 42 histologically reviewed classical MCL cases to determine the prognostic impact. VH3 was the most common VH family, with VH3-21 being the most frequent individual VH gene. Approximately 30% of the cases had a IgH somatic mutation rate higher than 2%, but was only higher than 4% in <10% of cases. Half of the cases had deletion of chromosome 11q21-telomere (11q21->ter), with two minimal deleted regions, at 11q22.2 and 11q23.2. There was no association between 11q loss and IgH gene somatic mutation rate; the use of VH3-21 gene could be associated with a better prognosis. [ABSTRACT FROM AUTHOR]

Background: Some studies evaluated the diagnostic performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography or positron emission tomography/computed tomography (PET or PET/CT) for the detection of post-transplant lymphoproliferative disorder (PTLD). As there is no clear consensus about the diagnostic accuracy of these imaging methods, we performed a meta-analysis on this topic. Methods: A comprehensive computer literature search of PubMed, Embase, and Cochrane library databases through December 2019 was performed. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−), and diagnostic odds ratio (DOR) of 18F-FDG PET or PET/CT for detection of PTLD were calculated. Results: Five studies reporting data on the diagnostic performance of 18F-FDG PET or PET/CT in 336 transplant recipients were included in the systematic review and bivariate meta-analysis. Pooled sensitivity and specificity for detection of PTLD were 89.7% (95% confidence interval (95%CI): 84.6–93.2%) and 90.9% (95%CI: 85.9–94.3%), respectively. Pooled LR+, LR−, and DOR were 8.9 (95%CI: 5.7–14), 0.13 (95%CI: 0.08–0.2), and 70.4 (95%CI: 35.4–140), respectively. A significant heterogeneity among studies was not detected. Conclusions: Despite limited literature data, 18F-FDG PET or PET/CT demonstrated good diagnostic performance for the detection of PTLD, but large prospective studies are needed to strengthen these findings. [ABSTRACT FROM AUTHOR]

Abstract: Rituximab maintenance therapy after effective induction has been shown to prolong progression-free and even overall survival, compared with no further treatment until relapse, in randomized, prospective phase III clinical trials in follicular lymphoma. In addition, the use of rituximab maintenance therapy is likely to have an important psychological and emotional impact for many patients. Currently, all patients are expected to relapse eventually following induction treatment: the knowledge that they are being actively treated to delay relapse for as long as possible may provide significant reassurance and emotional support. Similarly, the experience of relapse itself is also likely to be a traumatic event for patients: reducing the frequency of relapse with rituximab maintenance may thus spare patients some of this trauma. Overall, therefore, rituximab maintenance therapy might be expected to improve quality of life for patients with follicular lymphoma over and above the observed clinical benefits in progression-free and overall survival. At present, however, this can only be speculated from observations and experience. Formal quality-of-life and patient preference assessments will be required to demonstrate this conclusively. [Copyright &y& Elsevier]

Objective: Platinum-based chemotherapy plus the anti-EGFR monoclonal antibody (mAb) cetuximab is used to treat recurrent/metastatic (RM) head-neck squamous cell carcinoma (HNSCC). Recently, we defined Cluster3 gene-expression signature as a potential predictor of favorable progression-free survival (PFS) in cetuximab-treated RM-HNSCC patients and predictor of partial metabolic FDG-PET response in an afatinib window-of-opportunity trial. Another anti-EGFR-mAb (panitumumab) was used as the treatment agent in RM-HNSCC patients in the phase II PANI01trial. PANI01 tumor samples were analyzed using functional genomics to explore response predictors to anti-EGFR therapy.Materials and Methods: Whole-gene expression and real-time PCR analyses were applied to pre-treatment samples from 25 PANI01 patients. Three gene signatures (Cluster3 score, RAS onco-signature, microenvironment score) and seven selected miRNAs were separately analyzed for association with panitumumab efficacy.Results: Cluster3 expression levels had a profile with a significant bimodal separation of samples (P =  3.08 E-13). Higher RAS activation, microenvironment score, and miRNA expression were associated with low-Cluster3 patients. The same biomarkers were separately associated with PFS. Patients with high-Cluster3 had significantly longer PFS than patients with low-Cluster3 (median PFS: 174 versus 51 days; log-rank P = 0.0021). ROC analysis demonstrated accuracy in predicting PFS (AUC = 0.877).Conclusions: Despite differences in clinical settings and anti-EGFR inhibitors used for treatment, response prediction by the Cluster3 signature and selected miRNAs was essentially the same. Translation into a useful clinical assay requires validation in a broader setting. [ABSTRACT FROM AUTHOR]

Background Randomised trials of rituximab maintenance (MR) for patients with follicular lymphoma support improved progression-free survival (PFS), but the effect on overall survival has been inconclusive. To evaluate the effect of MR on overall survival according to patient and disease characteristics, and to explore certain adverse events, we performed an individual patient data (IPD) meta-analysis. Methods All investigators of randomised controlled trials that compared MR therapy with observation or treatment only at relapse (no MR) for patients with follicular lymphoma were invited to participate in an IPD meta-analysis. We obtained baseline patient and disease characteristics and time to progression and death for each patient. All analyses took into account the trial and original randomised treatment group. We analysed data in two ways: a two-stage analysis and a multivariate model including patient and disease characteristics. Findings Seven trials including 2315 patients were analysed. Overall survival of patients improved with MR compared with no MR (hazard ratio [HR] 0.79, 95% CI 0.66–0.96). We could not detect any patient or disease characteristics that were associated with a survival benefit with MR. In all of the models, MR had a beneficial effect on overall survival compared with observation for all types of patients, which was not shown in a particular subgroup in which the patient had already received rituximab in the induction phase and received first-line therapy. MR improved PFS compared with observation (HR 0.57, 95% CI 0.51–0.64). The risk of adverse events was higher with MR, specifically infection of any grade and grade 3–4 infections. Interpretation Based on IPD from randomised controlled trials, MR improves overall survival consistently in all patients, regardless of patient and disease characteristics when compared with observation, and should be prescribed after a successful induction with R-CVP or R-CHOP for patients with follicular lymphoma. It is still uncertain if that holds when the patient has already received rituximab in his/hers first induction. The effect of MR after bendamustine-rituximab induction compared with rituximab at progression should be further explored. [ABSTRACT FROM AUTHOR]

A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities. The revision clarifies the diagnosis and management of lesions at the very early stages of lymphomagenesis, refines the diagnostic criteria for some entities, details the expanding genetic/molecular landscape of numerous lymphoid neoplasms and their clinical correlates, and refers to investigations leading to more targeted therapeutic strategies. The major changes are reviewed with an emphasis on the most important advances in our understanding that impact our diagnostic approach, clinical expectations, and therapeutic strategies for the lymphoid neoplasms. [ABSTRACT FROM AUTHOR]

The article presents a study which reveals that Fc gamma receptor IIB decreases efficacy of rituximab monotherapy in treatment of follicular lymphoma (FL). Topics discussed include reduction in half life of antibody due to inhibitory FCGR2B, higher expression level of FCGR2B as compared to cells of FL and possible therapeutic significance of FCGR2B in lymphoid malignancies.

Summary Histological transformation ( HT) into diffuse large B-cell lymphoma ( DLBCL) was documented in 37 of the 281 (13%; 95% CI, 9-18) follicular lymphoma ( FL) patients treated at our institute from 1979 to 2007. HT occurred at a median of 2·75 years from initial FL diagnosis and HT rate was 15% at 10 years and 26% at 14 years, with a plateau from that point onward. Patients with bulky or extranodal disease, or those diagnosed before 1990 had a significantly higher risk of HT. When initial treatment strategies were taken into account, a reduced HT risk was seen in the patients initially managed with a 'watch and wait' policy, while the risk appeared significantly increased in the small subset of 18 patients initially managed with rituximab plus chemotherapy ( P = 0·0005). HT was associated with a significantly shorter cause-specific survival ( P = 0·0002). Predictors of survival after HT were the Follicular Lymphoma International Prognostic Index at diagnosis, as well as age and performance status at the time of HT. Our data confirm the adverse clinical outcome of FL after HT. In keeping with previous isolated reports, our findings suggest that there is a subgroup of patients in whom HT may not occur. [ABSTRACT FROM AUTHOR]

In a previous systematic review and meta-analysis of five randomized controlled trials comparing rituximab maintenance with no maintenance (observation or rituximab at progression) for patients with follicular lymphoma, we reported that rituximab maintenance treatment improved the overall survival of patients. In this study, we did a similar search of the electronic databases updated through December 31, 2010, and included nine trials and 2586 follicular lymphoma patients. Hazard ratios (HRs) for time-to-event data were estimated and pooled using the inverse variance method. Risk ratios for dichotomous data were pooled using a fixed effect model. Patients treated with rituximab maintenance had improved overall survival (pooled HR of death = 0.76, 95% confidence interval [CI] = 0.62 to 0.92) compared with patients in the no maintenance group. Patients with refractory or relapsed (ie, previously treated) follicular lymphoma treated with rituximab maintenance had improved overall survival (pooled HR of death = 0.72, 95% CI = 0.57 to 0.91), whereas previously untreated patients had no survival benefit (pooled HR of death = 0.86, 95% CI = 0.60 to 1.25). The rate of infection-related adverse events was higher in the rituximab maintenance group (pooled risk ratio = 1.67, 95% CI = 1.40 to 2.00). These results further support the use of rituximab maintenance in the standard of care for refractory or relapsed follicular lymphoma. [ABSTRACT FROM PUBLISHER]

Introduction/background: Leveraging the Follicular Lymphoma Analysis of Surrogacy Hypothesis database of individual patient data from first-line clinical trials, we studied the clinical course of follicular lymphoma (FL) and investigated clinical factors associated with FL outcomes., Patients and Methods: We examined 2428 patients from 8 randomized trials using multistate survival models with 4 states: induction treatment, progression, death from FL, and death from other causes. We utilized Aalen-Johansen estimator and Cox models to assess the likelihood of FL outcomes and quantify predictors' effects., Results: Two-year progression, FL-related death, and death from other causes estimates were 26.5%, 3.4% and 1.4%, respectively. FL-associated deaths were the primary cause of mortality within 10 years of follow-up. Male sex (hazard ratio: 1.25; 95% confidence interval: 1.05-1.47), > 4 involved nodal areas (1.51; 1.23-1.86), elevated LDH (1.20; 1.01-1.43), low hemoglobin (1.44; 1.15-1.81), and elevated β-2 levels (1.23; 1.02-1.47) increased risk of progression. CD20-targeting agents reduced risks for progression (0.29; 0.22-0.39), death from FL (0.05; 0.01-0.20), and death from other causes without progression (0.13; 0.05-0.33) and following progression (0.52; 0.30-0.92). Estimated 2-year progression rates were 22.3% and 43.5% with or without CD20-targeting agents, respectively. Two-year FL-associated mortality rate was 8.3% among patients without CD20-targeting agents, 5.4% with B-symptoms, 4.9% with elevated LDH, and 9.1% with low hemoglobin., Conclusion: This study identified independent contributions of baseline clinical factors to distinct outcomes for patients with FL following first-line therapy on a clinical trial. Similar analytical approaches are needed to increase understanding of factors that influence FL outcomes in other settings., (Copyright © 2022 Elsevier Inc. All rights reserved.)