179 research outputs found
Rituximab and autologous stem-cell transplantation for high-risk diffuse large B-cell lymphoma - Authors' reply
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Lenalidomide in Diffuse Large B-Cell Lymphomas
Diffuse Large B-cell Lymphomas (DLBCL) are the most frequent Non-Hodgkin Lymphomas (NHL). The addition of Rituximab to the standard chemotherapy CHOP improved the outcome in this patients, but so far 40% of patients experienced relapse or progressive disease. Lenalidomide, an immunomodulatory agent, had direct tumoricidal and antiangiogenetic actions on tumor cells and was able to modulate tumor-cell microenvironment, with the restoration of impaired T-cell activity and the formation of immuno-synapsis. Based on these actions, lenalidomide represented an active drug on aggressive relapsed NHL. In this review, the most relevant clinical trials for the use of lenalidomide in DLBCL were reported. Monotherapy with lenalidomide showed an activity in term of overall response rate, with acceptable hematological and extrahematological toxicities in relapsed/refractory aggressive NHL. The role of lenalidomide as salvage therapy in both cell of origin patterns in DLBCL (germinal center B-cell/activated B-cell) was reported in preliminary data. Preliminary data regarding the role of lenalidomide in addition to chemoimmunotherapy (R-CHOP) in first line clinical trials were discussed; data of safety, feasibility and efficacy were promising
A phase II study on the role of gemcitabine plus romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients
Background: There is no consensus regarding optimal treatment for peripheral T-cell lymphomas (PTCL), especially in relapsed or refractory cases, which have very poor prognosis and a dismal outcome, with 5-year overall survival of 30 %.
Methods: A multicenter prospective phase II trial was conducted to investigate the role of the combination of gemcitabine plus romidepsin (GEMRO regimen) in relapsed/refractory PTCL, looking for a potential synergistic effect of the two drugs. GEMRO regimen contemplates an induction with romidepsin plus gemcitabine for six 28-day cycles followed by maintenance with romidepsin for patients in at least partial remission. The primary endpoint was the overall response rate (ORR); secondary endpoints were survival, duration of response, and safety of the regimen.
Results: The ORR was 30 % (6/20) with 15 % (3) complete response (CR) rate. Two-year overall survival was 50 % and progression-free survival 11.2 %. Grade >= 3 adverse events were represented by thrombocytopenia (60 %), neutropenia (50 %), and anemia (20 %). Two patients are still in CR with median response duration of 18 months. The majority of non-hematological toxicities were mild and transient. No treatment-related death occurred and no toxicity led to treatment interruption.
Conclusions: GEMRO combination regimen shows efficacy data similar to those of single-agent romidepsin with additional hematologic toxicities. Synergy observed in preclinical phase did not turn into ability to improve clinical outcomes
Radiation Therapy in Primary Mediastinal B-Cell Lymphoma With Positron Emission Tomography Positivity After Rituximab Chemotherapy
Baseline total metabolic tumor volume is prognostic for refractoriness to Iimunochemotherapy in DLBCL: results from GOYA
Introduction
A good response to initial therapy is key to maximizing survival in patients with diffuse large B-cell lymphoma (DLBCL), but patients with chemorefractory disease and early progression have poor outcomes.
Patients and Methods
Data from the GOYA study in patients with DLBCL who received first-line rituximab or obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were analyzed. Positron emission tomography/computed tomography (PET/CT)-derived characteristics associated with total metabolic tumor volume (TMTV) and clinical risk factors for primary chemorefractory disease and disease progression within 12 months (POD12) were explored.
Results
Of those patients fulfilling the criteria for analysis, 108/1126 (10%) were primary chemorefractory and 147/1106 (13%) had POD12. Primary chemorefractory and POD12 status were strongly associated with reduced overall survival. After multivariable analysis of clinical and imaging-based risk factors by backward elimination, only very high TMTV (quartile [Q] 1 vs. Q4 odds ratio [OR]: 0.45; PâŻ=âŻ.006) and serum albumin levels (low vs. normal OR of 1.86; PâŻ=âŻ.004) were associated with primary chemorefractoriness. After additionally accounting for BCL2/MYC translocation in a subset of patients, TMTV and BCL2/MYC double-hit status remained as significant predictors of primary chemorefractoriness (Q1 vs. Q4 OR: 0.32, PâŻ=âŻ.01 and double-hit vs. no-hit OR of 4.47, PâŻ=âŻ.02, respectively). Risk factors including very high TMTV, high sum of the product of the longest diameters (SPD), geographic region (Asia), short time since diagnosis, extranodal involvement and low serum albumin were retained for POD12.
Conclusion
PET-derived TMTV has prognostic value in identifying patients at risk of early treatment failure
Evaluation of the effect of prospective biomarker testing on progression-free survival in diffuse large B-cell lymphoma.
Novel treatment regimens combining chemotherapy with targeted agents are being developed for diffuse large B-cell lymphoma (DLBCL). These regimens are expected to show efficacy in biomarker-defined..
Brentuximab vedotin in relapsed/refractory Hodgkin's lymphoma: the Italian experience and results of its use in daily clinical practice outside clinical trials
Clinical trial results indicate that brentuximab vedotin brings considerable promise for the treatment of patients with relapsed or refractory Hodgkin's lymphoma. A retrospective multicenter study was conducted on 65 heavily pretreated patients who underwent therapy through a Named Patient Program in Italy (non trial-setting). The primary study endpoint was the objective response rate; secondary endpoints were safety, overall survival and progression-free survival. The best overall response rate (70.7%), including 21.5% complete responses, was observed at the first restaging after the third cycle of treatment. After a median follow up of 13.2 months, the overall survival rate at 20 months was 73.8% while the progression-free survival rate at 20 months was 24.2%. Globally nine patients are in continuous complete response with a median follow up of 14 months (range, 10-19 months). Four patients proceeded to autotransplantation and nine to allotransplantation. The most frequent extra-hematologic toxicity was peripheral neuropathy, observed in 21.5% of cases (9 patients with grade 1/2 and 5 patients with grade 3/4); neurological toxicity led to discontinuation of treatment in three patients and to dose reduction in four. In general the treatment was well tolerated and toxicities, both hematologic and extra-hematologic, were manageable. This report indicates and confirms that brentuximab vedotin as a single agent is effective and safe also when used in standard, everyday clinical practice outside a clinical trial. Best overall responses were recorded after three or four cycles and showed that brentuximab vedotin provides an effective bridge to further therapeutic interventions
CNS relapse in patients with DLBCL treated with lenalidomide plus R-CHOP (R2CHOP): Analysis from two phase 2 studies
A prognostic model integrating PET-derived metrics and image texture analyses with clinical risk factors from GOYA
Image texture analysis (radiomics) uses radiographic images to quantify characteristics that may identify tumour heterogeneity and associated patient outcomes. Using fluoroâdeoxyâglucose positron emission tomography/computed tomography (FDGâPET/CT)âderived data, including quantitative metrics, image texture analysis and other clinical risk factors, we aimed to develop a prognostic model that predicts survival in patients with previously untreated diffuse large Bâcell lymphoma (DLBCL) from GOYA (NCT01287741). Image texture features and clinical risk factors were combined into a random forest model and compared with the international prognostic index (IPI) for DLBCL based on progressionâfree survival (PFS) and overall survival (OS) predictions. Baseline FDGâPET scans were available for 1263 patients, 832 patients of these were cellâofâorigin (COO)âevaluable. Patients were stratified by IPI or radiomics features plus clinical risk factors into lowâ, intermediateâ and highârisk groups. The random forest model with COO subgroups identified a clearer highârisk population (45% 2âyear PFS [95% confidence interval (CI) 40%â52%]; 65% 2âyear OS [95% CI 59%â71%]) than the IPI (58% 2âyear PFS [95% CI 50%â67%]; 69% 2âyear OS [95% CI 62%â77%]). This study confirms that standard clinical risk factors can be combined with PETâderived image texture features to provide an improved prognostic model predicting survival in untreated DLBCL
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