Follicular lymphoma at diagnosis, treated in first line with immunochemotherapy Data Acces Comitee
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PROVIDER: EGAC00001002912 | EGA |
REPOSITORIES: EGA
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Project description:We performed targeted NGS in Follicular lymphoma samples at diagnosis. Explored clinico-genetic correlations and assessed four clinical or clinicogenetic risk models (FLIPI, FLIPI-2, PRIMA-IP or m7-FLIPI-molecular score) in patients with symptomatic FL who received frontline immunochemotherapy. Out of 191 patients with FL grade 1-3a, 109 were successfully genotyped. Treatment consisted on rituximab (R) plus CVP/CHOP (72.5%) or R-bendamustine (R-B) (27.5%).
| EGAS00001006674 | EGA
Project description:Several clinical risk models have been proposed to predict the outcome of follicular lymphoma (FL). The development of next-generation sequencing technologies has allowed the integration of somatic gene mutations into clinical scores to build genotyped-based risk models, such as the m7-Follicular Lymphoma International Prognostic Index (FLIPI). We explored 4 clinical or clinicogenetic-risk models in patients with symptomatic FL who received frontline immunochemotherapy. Of 191 patients with FL grades 1 to 3a, 109 were successfully genotyped. The treatment consisted of rituximab (R) plus cyclophosphamide, vincristine, and prednisone (R-CVP)/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (72.5%) or R-bendamustine (R-B) (27.5%). The proportion of cases classified as high risk for FLIPI, FLIPI-2, PRIMA-prognostic index, or m7-FLIPI were 39.3%, 14%, 30.3%, and 22%, respectively. No case with low-intermediate FLIPI was upgraded in the m7-FLIPI, but 18 of the 42 high-risk patients with FLIPI were downgraded to low-risk m7-FLIPI. The sensitivity and specificity for the prediction of POD24 were highest for FLIPI. The discrimination between progression-free survival (PFS) and overall survival (OS) was the best for FLIPI (c-index: 0.644 and 0.727, respectively). When analyzed only in patients treated with R-B, m7-FLIPI showed a higher discrimination between PFS and OS. Thus, the FLIPI remains the clinical risk score with higher discrimination in patients with advanced FL treated with immunochemotherapy; however, the performance of the m7-FLIPI should be further investigated in patients treated with R-B.
| S-EPMC10173729 | biostudies-literature
Project description:AimsObinutuzumab (G) is a humanized type II, Fc-glycoengineered anti-CD20 monoclonal antibody used in various indications, including patients with previously untreated front-line follicular lymphoma. We investigated sources of variability in G exposure and association of progression-free survival (PFS) with average concentration over induction (CmeanIND ) in front-line follicular lymphoma patients treated with G plus chemotherapy (bendamustine, CHOP, or CVP) in the GALLIUM trial.MethodsIndividual exposures (CmeanIND ) were obtained from a previously established population pharmacokinetic model updated with GALLIUM data. Multivariate Cox proportional hazard models and univariate Kaplan-Meier plots investigated relationships of PFS with exposure and other potential prognostic factors.ResultsOverall, G exposure was lower in high body-weight patients and in males, and slightly lower in patients with high baseline tumour burden. Analysis of clinical outcomes showed that variability in G exposure did not impact PFS in G-bendamustine-treated patients; PFS was inferior in males and patients with FCGR2a/2b T232 T low-affinity receptor variant, and superior in patients with FCGR2a/2b I232T variant. In G-CHOP/CVP arms, PFS improved with increasing CmeanIND (hazard ratio = 1.74 and 0.394 at 5th and 95th percentile compared to median CmeanIND ) and was inferior in patients with high baseline tumour size and B symptoms.ConclusionsIt remains unclear whether for G-CHOP/CVP patients lower G exposure is a consequence of adverse disease biology and/or resistance to chemotherapy backbone (higher clearance in nonresponder patients, as demonstrated for rituximab) rather than being the cause of poorer clinical outcome. A study with >1 dose level of G could help resolve this uncertainty.
| S-EPMC6595360 | biostudies-literature
Project description:For the majority of patients with newly diagnosed follicular lymphoma (FL), current treatments, while not curative, allow for long remission durations. However, several important needs remain unaddressed. Studies have consistently shown that ∼20% of patients with FL experience disease progression within 2 years of first-line treatment, and consequently have a 50% risk of death in 5 years. Better characterization of this group of patients at diagnosis may provide insight into those in need of alternate or intensive therapies, facilitate a precision approach to inform clinical trials, and allow for improved patient counseling. Prognostic methods to date have employed clinical parameters, genomic methods, and a wide assortment of biological and biochemical markers, but none so far has been able to adequately identify this high-risk population. Advances in the first-line treatment of FL with chemoimmunotherapy have led to a median progression-free survival (PFS) of approximately 7 years; creating a challenge in the development of clinical trials where PFS is a primary end point. A surrogate end point that accurately predicts PFS would allow for new treatments to reach patients with FL sooner, or lessen toxicity, time, and expense to those patients requiring little to no therapy. Quality of response to treatment may predict PFS and overall survival in FL; as such complete response rates, either alone or in conjunction with PET imaging or minimal residual disease negativity, are being studied as surrogates, with complete response at 30 months after induction providing the strongest surrogacy evidence to date. A better understanding of how to optimize quality of life in the context of this chronic illness is another important focus deserving of further study. Ongoing efforts to address these important unmet needs are herein discussed.
| S-EPMC5834060 | biostudies-literature
Project description:Follicular lymphoma (FL) is a clinically and molecularly heterogeneous disease. Posttreatment surrogate end points, such as progression of disease within 24 months (POD24) are promising predictors for overall survival (OS) but are of limited clinical value, primarily because they cannot guide up-front treatment decisions. We used the clinical and molecular data from 2 independent cohorts of symptomatic patients in need of first-line immunochemotherapy (151 patients from a German Low-Grade Lymphoma Study Group [GLSG] trial and 107 patients from a population-based registry of the British Columbia Cancer Agency [BCCA]) to validate the predictive utility of POD24, and to evaluate the ability of pretreatment risk models to predict early treatment failure. POD24 occurred in 17% and 23% of evaluable GLSG and BCCA patients, with 5-year OS rates of 41% (vs 91% for those without POD24, P < .0001) and 26% (vs 86%, P < .0001), respectively. The m7-FL International Prognostic Index (m7-FLIPI), a prospective clinicogenetic risk model for failure-free survival, had the highest accuracy to predict POD24 (76% and 77%, respectively) with an odds ratio of 5.82 in GLSG (P = .00031) and 4.76 in BCCA patients (P = .0052). A clinicogenetic risk model specifically designed to predict POD24, the POD24-PI, had the highest sensitivity to predict POD24, but at the expense of a lower specificity. In conclusion, the m7-FLIPI prospectively identifies the smallest subgroup of patients (28% and 22%, respectively) at highest risk of early failure of first-line immunochemotherapy and death, including patients not fulfilling the POD24 criteria, and should be evaluated in prospective trials of precision medicine approaches in FL.
| S-EPMC5457130 | biostudies-other
Project description:This phase 2 study evaluated the activity and safety of ibrutinib, a Bruton's tyrosine kinase inhibitor, plus rituximab in adults with previously untreated follicular lymphoma. Patients received once-daily ibrutinib 560 mg continuously plus once-weekly rituximab 375 mg/m2 for 4 weeks beginning Week 1 (Arm 1, n = 60) or Week 9 (following an 8-week ibrutinib lead-in) to explore biomarkers (Arm 2, n = 20). The primary endpoint was the best overall response rate (ORR). The median age was 58 years; most had an Eastern Cooperative Oncology Group Performance Status of 0 (74%) and Stage III/IV disease (84%). At a median study follow-up of 34 months in Arm 1 and 29 months in Arm 2, ORRs were 85% [95% confidence interval (CI) 73-93] and 75% (95% CI 51-91), respectively, with complete responses in 40% and 50%. The median duration of response was not reached in either arm; 30-month progression-free and overall survival rates were 67% and 97% (Arm 1) and 65% and 100% (Arm 2). The most common adverse events were fatigue, diarrhoea and nausea. Higher grade (Grade 3/4) haematological, haemorrhagic and cardiac events occurred infrequently. Ibrutinib plus rituximab was active and tolerable in first-line follicular lymphoma.
| S-EPMC7317728 | biostudies-literature
Project description:The management of patients with relapsed or refractory follicular lymphoma has evolved markedly in the last decade, with the availability of new classes of agents (phosphoinositide 3-kinase inhibitors, immunomodulators, epigenetic therapies, and chimeric antigen receptor T cells) supplementing the multiple approaches already available (cytotoxic agents, anti-CD20 antibodies, radiation therapy, radioimmunotherapy, and autologous and allogeneic transplants). The diversity of clinical scenarios, the flood of data derived from phase II studies, and the lack of randomized studies comparing treatment strategies preclude firm recommendations and require personalized decisions. Patients with early progression require specific attention given the risk of histological transformation and their lower response to standard therapies. In sequencing therapies, one must consider prior treatment regimens and the potential need for future lines of therapy. Careful evaluation of risks and expected benefits of available options, which vary depending on location and socioeconomics, should be undertaken, and should incorporate the patient's goals. Preserving quality of life for these patients is essential, given the likelihood of years to decades of survival and the possibility of multiple lines of therapy. The current landscape is likely to continue evolving rapidly with other effective agents emerging (notably bispecific antibodies and other targeted therapies), and multiple combinations being evaluated. It is hoped that new treatments under development will achieve longer progression-free intervals and minimize toxicity. A better understanding of disease biology and the mechanisms of these different agents should provide further insights to select the optimal therapy at each stage of disease.
| S-EPMC8719064 | biostudies-literature
Project description:Background: Follicular lymphoma (FL) is an indolent malignancy of germinal center B cells with highly variable patient outcomes. Recently, a 23-gene predictor score was proposed for predicting progression-free survival. In the past, we had shown that the m7-FLIPI, a clinico-genetic risk model, allows to improve patient stratification compared to clinical risk models alone. The multitude of prognostic tools in FL raises the question whether they identify common biology. Methods: In this study, we applied a modified risk score (MRS) to an independent gene-expression dataset of FL patients treated with rituximab in combination with chemotherapy. Results: Using supervised and unsupervised approaches, we showed that the MRS identifies patient groups with diverging outcomes in our dataset. In addition, using gene set enrichment and network identification, we discovered associations between the MRS, the m7-FLIPI, EZH2 mutation status and FOXP1 expression. Conclusions: Our findings lend support to expression of dark-zone related genes as a key determinant of poor outcome following rituximab and chemotherapy.
2019-02-19 | GSE119214 | GEO
Project description:PurposeRituximab (R) or obinutuzumab (G) combined with CHOP chemotherapy are used in previously untreated follicular lymphoma (FL). The aim is to compare in real life setting the efficacy and safety of these therapeutic strategies and assess the economic impact of introducing G.MethodsThis retrospective study, performed in 3 centers, included data from all patients who received R-CHOP or G-CHOP for previous untreated FL from June 1st, 2016 to December 31st, 2020. Progression-Free Survival (PFS) were estimated according to the Kaplan-Meier method. A budgetary impact model was performed from the French health care system's perspective.ResultsN = 124 patients were included (58 G-CHOP; 66 R-CHOP). Fifty-one and 57 patients achieved a complete response at the end of induction in the G-CHOP and R-CHOP group, respectively. PFS was not significantly longer in the G-CHOP group (HR 0.28; 95% CI 0.08-0.97; p value = 0.14). Hematological toxicity occurred more frequently with G-CHOP than R-CHOP during induction treatment (n = 58; 100% vs. n = 61; 92%), including higher severe neutropenia (grade ≥ 3) (n = 26; 45% vs. n = 23; 35%). Infusion-related reactions during the first infusion occurred more frequently with G-CHOP (n = 19; 33% vs. n = 16; 24%). The introduction of a completed G treatment (induction and maintenance) results in an additional cumulative cost per patient estimated at more than €30,000.ConclusionSimilar results were found in the GALLIUM subgroup analysis study, suggesting that at this time there is no absolute benefit to administer G-CHOP instead of R-CHOP in all patients with previously untreated FL and may encourage clinical and economic trials including quality of life data.
| S-EPMC9255466 | biostudies-literature
Project description:Background/aimsReal-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).MethodsA 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.ResultsOf 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.ConclusionThe 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