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Predictors of local recurrence after rituximab-based chemotherapy alone in stage III and IV diffuse large B-cell lymphoma: guiding decisions for consolidative radiation.

ABSTRACT: The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT.Two hundred eleven patients with stage III and IV DLBCL treated between August 1999 and January 2012 were reviewed. Of these, 89 had a complete response to systemic therapy including rituximab and received no initial RT. Kaplan-Meier analysis and Cox proportional hazards regression were performed, with local recurrence (LR) as the primary outcome.The median follow-up time was 43.9 months. Fifty percent of patients experienced LR at 5 years. In multivariate analysis, tumor ? 5 cm and stage III disease were associated with increased risk of LR. The 5-year LR-free survival was 47.4% for patients with ? 5-cm lesions versus 74.7% for patients with <5-cm lesions (P=.01). In patients with <5-cm tumors, the maximum standardized uptake value (SUVmax) was ? 15 in all patients with LR. The 5-year LR-free survival was 100% in SUV<15 versus 68.8% in SUV ? 15 (P=.10).Advanced-stage DLBCL patients with stage III disease or with disease ? 5 cm appear to be at an increased risk for LR. Patients with <5-cm disease and SUVmax ? 15 may be at higher risk for LR. These patients may benefit from consolidative RT after chemoimmunotherapy.

SUBMITTER: Jegadeesh N

PROVIDER: S-EPMC4394239 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Predictors of local recurrence after rituximab-based chemotherapy alone in stage III and IV diffuse large B-cell lymphoma: guiding decisions for consolidative radiation.

Jegadeesh Naresh N Rajpara Raj R Esiashvili Natia N Shi Zheng Z Liu Yuan Y Okwan-Duodu Derrick D Flowers Christopher R CR Khan Mohammad K MK

International journal of radiation oncology, biology, physics 20150501 1

<h4>Purpose</h4>The role of consolidative radiation therapy (RT) for stage III and IV diffuse large B-cell lymphoma (DLBCL) in the era of rituximab is not well defined. There is evidence that some patients with bulky disease may benefit, but patient selection criteria are not well established. We sought to identify a subset of patients who experienced a high local failure rate after receiving rituximab-based chemotherapy alone and hence may benefit from the addition of consolidative RT.<h4>Metho ...[more]

PMID: 25863758

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Project description:BackgroundRituximab has been shown to improve response rates and progression free survival when added to chemotherapy in patients with indolent and mantle cell lymphoma. However, the impact of R on overall survival (OS) when given in combination with chemotherapy (R-chemo) has remained unclear so far.ObjectivesWe thus performed a comprehensive systematic review in this group of patients to compare R-chemo with chemotherapy alone with respect to OS. Other endpoints were overall response rate (ORR), toxicity and disease control as assessed by measures such as time to treatment failure (TTF), event free-survival (EFS), progression free-survival (PFS) and time to progression (TTP).Search strategyWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and conference proceeding from 1990 to 2005.Selection criteriaOnly randomised controlled trials (RCT) comparing R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed indolent lymphoma and mantle cell lymphoma (MCL) were included.Data collection and analysisTwo review authors extracted data and assessed the study quality. Number needed to treat (NNT) were calculated to facilitate interpretation.Main resultsSeven randomised controlled trials involving 1943 patients with follicular lymphoma, mantle cell lymphoma, or other indolent lymphomas were included in the meta-analysis. Five studies were published as full-text articles, and two were in abstract form. Patients treated with R-chemo had better overall survival (hazard ratio [HR] for mortality 0.65; 95% confidence interval (CI) 0.54 to 0.78), overall response (relative risk of tumour response 1.21; 95% CI 1.16 to 1.27), and disease control (HR of disease event 0.62; 95% CI 0.55 to 0.71) than patients treated with chemotherapy alone. R-chemo improved overall survival in patients with follicular lymphoma (HR for mortality 0.63; 95% CI 0.51 to 0.79) and in patients with mantle cell lymphoma (HR for mortality 0.60; 95% CI 0.37 to 0.98). However, in the latter case, there was heterogeneity among the trials (P 0.07), making the survival benefit less reliable.Authors' conclusionsThe systematic review demonstrated improved OS for patients with indolent lymphoma, particularly in the subgroups of follicular and in mantle cell lymphoma when treated with R-chemo compared to chemotherapy alone.

Project description:PurposeThe addition of rituximab to standard chemotherapy has significantly improved survival in patients with lymphoma. Recently, maintenance therapy with rituximab has been shown to prevent relapse and provide survival benefits for patients with follicular or mantle cell lymphoma. However, the effects of rituximab in patients with diffuse large B-cell lymphoma (DLBCL) remain unclear. Two new studies involving rituximab in the treatment of DLBCL were performed this past year. We performed a meta analysis to evaluate the effects of rituximab maintenance treatment of patients with DLBCL.MethodsSeveral databases (PubMed, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) databases were reviewed for relevant randomized controlled trials published prior to May, 2016. Two reviewers assessed the quality of the included studies and extracted data independently. The hazard ratios (HRs) for time-to-event data and relative risks (RRs) for the other data were pooled and estimated.ResultsTotally 5 studies including 1740 patients were eligible for the meta-analysis. Compared to the observation group, patients who received rituximab maintenance therapy had significantly improved event-free survival (EFS) (HR = 0.80, 95% CI: 0.65-0.98) and progression-free survival (PFS) (HR = 0.72, 95% CI: 0.54-0.94). However, there was no statistically significant difference in overall survival (OS) (HR = 0.66, 95% CI: 0.27-1.29). A subgroup analysis suggested that male patients may benefit from rituximab maintenance therapy with a better EFS (HR = 0.53, 95% CI: 0.34-0.82-), while this advantage was not observed in female patients (HR = 0.99, 95% CI: 0.64-1.52).ConclusionsRituximab maintenance may provide survival benefits beyond that afforded by first- and second-line chemotherapy alone, especially in male patients. However, maintenance rituximab treatment may cause more adverse events. It is recommended that both survival benefits and adverse events should be taken into consideration when making treatment decisions.

Dataset Information

Predictors of local recurrence after rituximab-based chemotherapy alone in stage III and IV diffuse large B-cell lymphoma: guiding decisions for consolidative radiation.

Publications

Predictors of local recurrence after rituximab-based chemotherapy alone in stage III and IV diffuse large B-cell lymphoma: guiding decisions for consolidative radiation.

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