A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma.

We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P<0.0001). Neither the mantle cell lymphoma index, nor fluorodeoxyglucose-positron emission tomography nor Ki67 positivity (cut off of ≥30%) showed a prognostic impact for survival. Hematologic grade 3-4 toxicities were mainly neutropenia (51%), thrombocytopenia (35%) and lymphopenia (65%). Grade 3-4 non-hematologic toxicities were mainly fatigue (18.5%), neuropathy (15%) and infections. In conclusion, the tested treatment regimen is active as frontline therapy in older patients with mantle cell lymphoma, with manageable toxicity. Minimal residual disease status after induction could serve as an early predictor of survival in mantle cell lymphoma. ClinicalTrials.gov: NCT 01457144.

Analyses of patterns-of-failure and prognostic factors according to radiation fields in early-stage Hodgkin lymphoma.

PURPOSE: Doses and volumes of radiation therapy (RT) for early stages of Hodgkin lymphoma (HL) have been reduced over the last 30 years. Combined modality therapy (CMT) is currently the standard treatment for most patients with early-stage HL. The aim of this study was to analyze the site of relapse after RT according to the extent of radiation fields. PATIENTS AND METHODS: Between 1987 and 2011, 427 patients were treated at our institution with RT ± chemotherapy for stage-I/II HL. Among these, 65 patients who experienced a relapse were retrospectively analyzed. Most patients had nodular sclerosis histology (86 %) and stage-II disease (75.9 %). Bulky disease was present in 21 % and 56 % of patients belonged to the unfavorable risk group according to European Organization for Research and Treatment of Cancer (EORTC)/The Lymphoma Study Association (LYSA) definitions. CMT was delivered to 91 % of patients. All patients received RT with doses ranging from 20 to 45 Gy (mean = 34 ± 5.3 Gy). The involved-field RT technique was used in 59 % of patients. RESULTS: The mean time between diagnosis and relapse was 4.2 years (range 0.3-24.5). Out-of-field relapses were suffered by 53 % of patients. Relapses occurred more frequently at out-of-field sites in patients with a favorable disease status, whereas in-field relapses were associated with bulky mediastinal disease. Relapses occurred later for favorable compared with the unfavorable risk group (3.5 vs. 2.9 years, p = 0.5). From multivariate analyses, neither RT dose nor RT field size were predictive for an in-field relapse (p = 0.25 and p = 0.8, respectively), only bulky disease was predictive (p = 0.018). CONCLUSION: In patients with bulky disease, RT dose and RT field size were not predictive for an in-field relapse. In this subgroup of patients, chemotherapy should be intensified. We confirmed the bad prognosis of early relapses.

Long-term follow-up analysis of 100 patients with splenic marginal zone lymphoma treated with splenectomy as first-line treatment.

Splenectomy is considered as one of the first-line treatments for symptomatic patients with splenic marginal zone lymphoma (SMZL). Between 1997 and 2012, 100 hepatitis C virus-negative patients with SMZL were treated by splenectomy as first-line treatment. At 6 months, all patients but three recovered from all cytopenias. The median lymphocyte count at 6 months and 1 year was 11.51 × 10(9)/L and 6.9 × 10(9)/L, respectively. Median progression-free survival (PFS) was 8.25 years. The 5-year and 10-year overall survival (OS) rates were 84% and 67%, respectively. Histological transformation occurred in 11% of patients, and was the only parameter significantly associated with a shorter time to progression (p = 0.0001). Significant prognostic factors for OS were age (p = 0.0356) and histological transformation (p = 0.0312). In this large retrospective cohort, we confirmed that splenectomy as first-line treatment in patients with SMZL corrected cytopenias and lymphocytosis within the first year and was associated with a good PFS.