Rituximab maintenance therapy after transplantation prolonged event-free survival, progression-free survival, and overall survival among patients with mantle-cell lymphoma who were younger than 66 years of age at diagnosis. (Funded by Roche and Amgen; LyMa ClinicalTrials.gov number, NCT00921414 .).

International audienceChronic myelomonocytic leukemia (CMML) is a haematological disease currently classified in the category of myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) because of its dual clinical and biological presentation. The molecular biology of CMML is poorly characterized. We studied a series of 53 CMML samples including 31 cases of myeloproliferative form (MP-CMML) and 22 cases of myelodysplastic forms (MD-CMML) using array-comparative genomic hybridization (aCGH) and sequencing of 13 candidate genes including ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, PTPN11, RUNX1, TET2 and WT1. Mutations in ASXL1 and in the genes associated with proliferation (CBL, FLT3, PTPN11, RAS) were mainly found in MP-CMML cases. Mutations of ASXL1 correlated with an evolution toward an acutely transformed state: all CMMLs that progressed to acute phase were mutated and none of the unmutated patients had evolved to acute leukaemia. The overall survival of ASXL1 mutated patients was lower than that of unmutated patients

Purpose Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. Patients and Methods Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC]). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. Results From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% ( P = .01). The proportional hazards assumption was rejected for OS ( P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively ( P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm ( P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm ( P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm ( P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm ( P = .04), and fewer patients required a second treatment after ICL. Conclusion Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.

Objectives The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial. Methods The trial enrolled 424 patients with de novo AML. Among them, 316 benefited from geriatric assessment (GA) including nutritional, cognitive, and functional status and were scored according to Eastern Cooperative Oncology Group (ECOG) and sorror for the prediction of treatment toxicity, morbidity, and mortality. Patients were investigated at diagnosis for three times during follow‐up. Results This study showed that AML and its treatment have no impact on cognitive (P = .554) nor functional status (P = .842 for Activity of Daily Living and P = .087 for Instrumental Activities of Daily Living). The nutritional status improved over time (P = .041). None of these three parameters at baseline, associated or not with ECOG and sorror scores, impacted survivals or toxicities. Conclusions The cognitive, functional, and nutritional status had no impact in this cohort of fit elderly AML patients without unfavorable cytogenetics. The GA tools used provided no additional information compared with ECOG and sorror scores, to predict toxicity, morbidity, or mortality due to intensive chemotherapy.

We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for mantle cell lymphoma patients of 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of 6 treatment cycles at 28 day intervals. The primary objective was to achieve an 18 month progression-free-survival of ≥ to 65%. Secondary objectives were to evaluate toxicity and the mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow, for prognostic impact. With a median follow-up of 52 months, the 24 month progression free survival rate was 70%, hence the primary objective was reached. After 6 cycles, 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, for blood molecular residual disease negative patients at treatment end, were 86.6% and 28.6%, respectively (P< 0.0001). Neither the mantle cell lymphoma index, fluorodeoxyglucose-positron emission tomography nor Ki67 positivity (cut off of ≥ 30%) showed prognostic impact for survival. Hematological grade 3-4 toxicities were mainly neutropenia (51%), thrombocytopenia (35%) and lymphopenia (65%). Grade 3-4 non-hematological toxicities were mainly fatigue (18.5%), neuropathy (15%) and infections. In conclusion, this treatment regimen is active for frontline therapy in older patients with mantle cell lymphoma, with manageable toxicity. Minimal residual disease status after induction could serve as an early predictor for survival in mantle cell lymphoma. ClinicalTrials.gov: NCT 01457144.