• The complete response rate for first-line bendamustine/ rituximab was statistically noninferior to R-CHOP or R-CVP in indolent NHL or MCL.• The safety profile of bendamustine/rituximab is distinct from that of R-CHOP/ R-CVP.This randomized, noninferiority (NI), global, phase 3 study evaluated the efficacy and safety of bendamustine plus rituximab (BR) vs a standard rituximab-chemotherapy regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] or rituximab plus cyclophosphamide, vincristine, and prednisone [R-CVP]) for treatmentnaive patients with indolent non-Hodgkin's lymphoma or mantle cell lymphoma. Investigators preassigned the standard treatment regimen they considered most appropriate for each patient; patients were randomized to receive BR (n 5 224) or standard therapy (R-CHOP/R-CVP, n 5 223) for 6 cycles; 2 additional cycles were permitted at investigator discretion. Response was assessed by a blinded independent review committee. BR was noninferior to R-CHOP/R-CVP, as assessed by the primary end point of complete response rate (31% vs 25%, respectively; P 5 .0225 for NI [0.88 margin]). The overall response rates for BR and R-CHOP/R-CVP were 97% and 91%, respectively (P 5 .0102). Incidences of vomiting and drug-hypersensitivity reactions were significantly higher in patients treated with BR (P < .05), and incidences of peripheral neuropathy/paresthesia and alopecia were significantly higher in patients treated with standard-therapy regimens (P < .05). These data indicate BR is noninferior to standard therapy with regard to clinical response with an acceptable safety profile.

We analyzed the safety and efficacy of Mylotarg (gemtuzumab ozogamicin, an antibody-targeted chemotherapy consisting of a humanized anti-CD33 antibody linked to calicheamicin, a potent antitumor antibiotic) in the treatment of 101 patients Ն60 years of age with acute myeloid leukemia (AML) in untreated first relapse in three open-label trials. Mylotarg is administered as a 2-h intravenous infusion at 9 mg/m 2 for two doses with 14 days between doses. The overall remission rate was 28%, with complete remission (CR) in 13% of patients and complete remission with incomplete platelet recovery (CRp) in 15%. Median survival was 5.4 months for all patients and 14.5 months and 11.8 months for patients achieving CR and CRp, respectively. CD33 antigen is present on normal hematopoietic progenitor cells; thus, an expected high incidence of grade 3 or 4 neutropenia (99%) and thrombocytopenia (99%) was observed. The incidences of grade 3 or 4 elevations of bilirubin and hepatic transaminases were 24% and 15%, respectively. There was a low incidence of grade 3 or 4 mucositis (4%) and infections (27%) and no treatment-related cardiotoxicity, cerebellar toxicity, or alopecia. Mylotarg is an effective treatment for older patients with CD33-positive AML in first relapse and has acceptable toxicity.

in association with the Biotherapy Development Association Abstract Purpose: A fully human monoclonal antibody to anti^a v integrins (CNTO 95) has been shown to inhibit angiogenesis and tumor growth in preclinical studies. We assessed the safety and pharmacokinetics of CNTO 95 in patients with advanced refractory solid tumors. Experimental Design: In this phase I trial, CNTO 95 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg) was infused on days 0, 28, 35, and 42, and clinical assessments, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and [18 F]-2-fluorodeoxyglucose positron emission tomography (FDG-PET) were done. Patients achieving stable disease or better were eligible for extended dosing every 3 weeks for up to 12 months. Results: Among the 24 enrolled patients, CNTO 95 was associated with one episode of grade III and four episodes of grade II infusion-related fever (all responded to acetaminophen). Of the six patients who received extended dosing, one patient (10.0 mg/kg), with cutaneous angiosarcoma, had a 9-month partial response. Pre-and post-treatment lesion biopsies confirmed tumor cell a v integrin expression, as well as CNTO 95 penetration of the tumor and localization to tumor cells in association with reduced bcl-2 expression. A lesion in one patient (10.0 mg/kg) with stable ovarian carcinosarcoma was no longer detectable by FDG-PET by day 49. Exposure to CNTO 95 seemed to increase in a greater-than-dose-proportional manner; dose-dependent mean halflife ranged from 0.26 to 6.7 days. Conclusions: CNTO 95 was generally well tolerated. Six patients received extended therapy, including one patient with a prolonged response. Biopsy data confirmed tumor localization and pharmacodynamic activity.

We show, in this first-ever report of increased arterial stiffness in children on dialysis, that end-stage renal disease is associated with abnormalities in arterial wall elastic properties, comparable with adult levels, even in childhood. Most importantly, the absence of a discernible amelioration with dialysis implies that purely structural and not functional alterations lie behind the increased arterial stiffness.

Background Omacetaxine, a protein synthesis inhibitor, is indicated in the US for the treatment of patients with chronic (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Methods This final analysis, with 24-month follow-up, includes additional efficacy and safety analyses to assess the benefit of long-term omacetaxine administration (1.25 mg/m2 bid for 14 days q 28 days followed by 7 days q 28 days) in CP- and AP-CML patients receiving >3 cycles. Results Eighteen percent of CP-CML patients achieved major cytogenetic response (MCyR) with a median duration 12.5 months (95% confidence interval [CI], 3.5-not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders and median overall survival (OS) was 40.3 months (95% CI, 23.8-not reached). In patients with AP-CML, 14% achieved or maintained major hematologic response for a median of 4.7 months (95% CI, 3.6-NR); MCyR was not achieved and median OS was 14.3 months (95% CI, 6.7–18.7). In patients with CP- or AP-CML who received >3 cycles of treatment (n=50 and 14, respectively), median OS was 49.3 months (95% CI, 23.8-NR) and 24.6 months (95% CI, 12–37.2), respectively. Grade ≥3 hematologic toxicity was the major side effect (79%/73% in CP-CML/AP-CML), with discontinuation due to toxicity in 10% of CP and 5% of AP patients. Conclusions These results suggest that long-term administration of omacetaxine is feasible with dose adjustments to manage toxicities, and that omacetaxine provides durable benefit in some patients.