ALBERT

Description: Introduction: Chronic Lymphocytic Leukemia (CLL) is the most frequent adult leukemia in western countries. It is known to have a heterogeneous clinical course, some patients presenting an indolent disease while others have an aggressive disease requiring prompt treatment. Therefore, an individualized approach, especially in early clinical stage patients is necessary. Recent studies suggest that the biological markers LPL and ADAM-29 could be useful to predict prognosis in CLL patients: LPL being associated with an unfavorable prognosis while ADAM-29 to favorable one. Aims: to evaluate the expression of LPL (L), ADAM-29 (A) and the L/A ratio in CLL patients in regard to Binet clinical stage and progression free survival (PFS). Patients and Methods: thirty CLL patients followed at UNIFESP/EPM and HSPE were studied. RNA extraction was done by the TRIZOL method followed by c-DNA synthesis. c-DNA was amplified by PCR using LPL and ADAM-29 specific primers. T-Student’s exact test was used to compare the genes frequencies and Kaplan Meyer analysis to evaluate PFS. The results were considered statistically significant when p

Description: Introduction: Chronic Lymphocytic Leukemia (CLL) is the most frequent leukemia in adults of western countries. Its clinical course is variable with some patients presenting an indolent disease while others have an aggressive disease requiring prompt treatment. Biomarkers to identify patients with poor prognosis, especially in early clinical stages, are being studied. Increase of angiogenesis, as an apoptosis deregulator, has been associated to poor prognosis in some malignant diseases such as Multiple Myeloma and Non-Hodgkin Lymphoma. Expression of Vascular Endothelial Growth Factor (VEGF) in CLL cells seems to have an unfavorable impact on prognosis, even though only a few studies have addressed this issue. AIMS: to analyze the expression of VEGF and its relation to Binet clinical stage, mutation status of IgVH and event free survival. Patients and Methods: 52 CLL patients diagnosed at UNIFESP and HSPE were studied. VEGF expression was evaluated on blood samples stained with Biotinylated Human VEGF (R&D Systems) monoclonal antibody and acquired with FACScalibur® and analyzed CellQuest® software. The expression of VEGF was considered positive when its mean fluorescence intensity was 〉200. IgVH mutation of 25 cases status was also studied by sequencing of the amplified samples by RT-PCR using VH family specific primers. The sequences were analysed with lg Blast® software and considered mutated (M) when there was a germline homology of 98% or greater and those displaying homology

Description: Background Rituximab is part of the standard induction and maintenance therapy for most patients with first-line or relapsing indolent non-Hodgkin's lymphoma (iNHL). However, the optimal duration of maintenance is still to be defined. The MABCUTE trial is designed to evaluate the efficacy and safety of maintenance therapy with subcutaneous (SC) rituximab until disease progression (PD). Patients with relapsed or refractory iNHL, who respond to induction and an initial 2 years' maintenance therapy, are randomized to receive additional maintenance therapy or observation. Here we report the findings of a planned interim safety analysis in the first 231 patients enrolled in the trial. Methods MABCUTE (NCT01461928) is an ongoing multicenter, randomized, parallel-group, phase IIIb study that started in December 2011. Eligible patients were aged ≥18 years with relapsed or refractory CD20+ iNHL (histologically confirmed) following ≥1 line of immunotherapy and/or chemotherapy and/or radiotherapy. Patients were scheduled to receive induction therapy consisting of rituximab every 3–4 weeks for 8 cycles (intravenous [IV] 375 mg/m2 in cycle 1 then SC 1400 mg in cycles 2–8) and 6–8 cycles of standard chemotherapy. Patients who achieved a complete or partial response (CR/PR) continued into standard maintenance (rituximab SC 1400 mg every 8 weeks for 24 months). Upon completion of standard maintenance, patients in sustained CR/PR will be randomized to receive additional maintenance (rituximab SC 1400 mg every 8 weeks) until PD, or observation. Results At data cut-off (January 16, 2013), the safety population consisted of 216 patients who had received ≥1 dose of rituximab SC: 70 (32%) had completed induction therapy, 122 (57%) were receiving induction therapy, and 24 (11%) had discontinued induction therapy. A total of 58 (27%) patients had continued into standard maintenance, with 2 patients having subsequently discontinued maintenance therapy. Patients had a median age of 64.5 years (range, 20–90). At screening, the most common types of iNHL were follicular NHL (n=131, 61%), marginal zone lymphoma (n=41, 19%), and Waldenström's macroglobulinemia (n=31, 14%). The most commonly used chemotherapy regimens were bendamustine (n=137, 63%), CHOP (n=31, 14%) and CVP (n=21, 9.7%). During therapy, AEs occurred in 174 (81%) patients (Table), grade 3 or higher AEs in 70 (32%) patients and serious AEs (SAEs) in 44 (20%) patients. Administration-related reactions (ARRs) were reported by 61 (28%) patients after 1 dose of rituximab IV and by 89 (41%) patients after a median (range) of 5 (1–11) doses of rituximab SC. The majority of ARRs were mild to moderate and transient, and expected with the change in the route of administration. Overall, 25 patients had grade 4 hematological events, most commonly neutropenia (22 patients). Only 4 cases of neutropenia lasted 〉14 days and these resolved without interruption to treatment. One patient had a grade 4 non-hematological event (thrombosis and pulmonary embolism that resolved after 12 days). Among the 26 patients who discontinued study treatment, reasons given were AEs (n=8; skin reactions [3], neutropenia [2], general health problems [2], and oseophagitis [1]), patient or investigator request (n=6), PD (n=5), death (n=2), and other (n=5). One patient died of bronchopneumonia and sepsis due to leucopenia and 1 died of myocarditis; neither was considered by the investigator to be related to the study drug. Conclusions Rituximab SC is associated with ARRs that are transient and mainly mild to moderate in severity. The incidence and intensity of other hematological and non-hematological toxicities are within the expected range for rituximab SC or IV administration. No new safety signals or concerns associated with rituximab SC were identified during induction and maintenance therapy in this interim safety analysis, as confirmed by the Independent Data Monitoring Committee. Rituximab SC appears to be well tolerated and the study continues. Disclosures: Rule: Pharmacyclics, Inc: Consultancy; J&J: Consultancy; F. Hoffmann-La Roche: Consultancy. Off Label Use: Rituximab, administered as an IV infusion, is approved for use in a number of hematologic indications. The data presented here assess a subcutaneous approach to rituximab administration in patients with indolent Non-Hodgkin’s Lymphoma. Briones:Celgene: Membership on an entity’s Board of Directors or advisory committees; Takeda: Membership on an entity’s Board of Directors or advisory committees; Novartris: Membership on an entity’s Board of Directors or advisory committees; F. Hoffmann-La Roche: Honoraria. Casasnovas:F. Hoffmann-La Roche: Consultancy, Research Funding. Pocock:F. Hoffmann-La Roche: Honoraria. Osborne:F. Hoffmann-La Roche: Employment. Smith:F. Hoffmann-La Roche: Employment. Zaja:F. Hoffmann-La Roche: Consultancy.