Emerging Pharmacotherapy for Relapsed or Refractory Hodgkin’s Lymphoma: Focus on Brentuximab Vedotin

Hodgkins’ lymphoma (HL) which has relapsed post or is refractory to autologous bone marrow transplant presents an ongoing treatment challenge. Development of monoclonal antibodies (mAb) for the treatment of HL has aimed to replicate the success of mAb therapy in the treatment on Non Hodgkins Lymphoma. The identification of CD30 as a potential target for treatment has led to the development of a new antibody-drug conjugate, brentuximab vedotin (SGN-35), which conjugates monomethyl auristatin E to an anti-CD30 antibody to deliver targeted toxicity to the malignant Reed Sternberg cells of HL. This review describes CD30 as an antibody target, and focuses on the antibody-drug conjugate brentuximab vedotin, including current knowledge of the mechanism of action, preclinical, clinical and pharmacokinetic data available for Brentuximab Vedotin

Tracing the evolution of nearby early-type galaxies in low density environments. The Ultraviolet view from GALEX

We detected recent star formation in nearby early-type galaxies located in low density environments, with GALEX Ultraviolet (UV) imaging. Signatures of star formation may be present in the nucleus and in outer rings/arm like structures. Our study suggests that such star formation may be induced by different triggering mechanisms, such as the inner secular evolution driven by bars, and minor accretion phenomena. We investigate the nature of the (FUV-NUV) color vs. Mg2 correlation, and suggest that it relates to "downsizing" in galaxy formation.Comment: Conference "UV Universe 2010" S. Petersburg 31 May - 3 June, 2010 Accepted for publication in Astrophysics & Space Science . The final publication is available at http://www.springerlink.co

1083P - Peripheral Blood Stem Cell (PBSC) Mobilization and Engraftment after Brentuximab Vedotin Treatment in Anaplastic Large Cell Lymphoma (ALCL) Patients

Brentuximab vedotin is a CD30-targeted antibody conjugated to the microtubule-disrupting agent, monomethyl auristatin E (MMAE), by a protease-cleavable linker. In a pivotal phase 2 study (ClinicalTrials.gov NCT00866047), an objective response was achieved in 50 of 58 (86%) relapsed/refractory ALCL patients (pts) treated with brentuximab vedotin. More than half of the pts achieved a complete remission (CR) (59%), enabling some pts to subsequently receive a stem cell transplant (SCT) as consolidation. A retrospective evaluation was performed to characterize PBSC mobilization and engraftment following brentuximab vedotin treatment (tx). Pts received 1.8 mg/kg brentuximab vedotin every 3 weeks as a 30-minute outpatient IV infusion for up to 16 cycles. Antitumor efficacy was based on response assessments by independent review according to Cheson 2007. Eight pts received autologous SCT as the first therapy after discontinuing tx with brentuximab vedotin in remission. PBSC collection was completed prior to initiation of brentuximab vedotin tx in 2 pts, and following brentuximab vedotin tx in 6 pts. These 6 pts achieved a best clinical response of CR with brentuximab vedotin tx. After brentuximab vedotin tx, PBSCs were mobilized using chemomobilization (n = 3 pts), plerixafor (n = 1), and granulocyte colony-stimulating factor alone (G-CSF) (n = 2). The number of CD34+ cells/kg obtained and the days of collection are shown in the table. The CD34 + /kg yield for each pt was greater than the standard target of ≥2.5x106, with a median of 7.0x106. All pts engrafted, and the median time to engraftment was 10.5 days (range 9–14) for neutrophils and 11.5 days (range 9–13) for platelets. The 100-day mortality rate post SCT was 0%. Brentuximab vedotin does not appear to have a negative impact on the outcome of PBSC mobilization or engraftment in pts receiving high-dose therapy and auto SCT.Unlabelled TableAgeSexCycles of B-VMobilization RegimenDays CollectedCD34+ Cells/kg (x 106)46M4IE/GCSF146.957F8IE/GCSF27.161M7plerixafor44.141F8GCSF26.950F8CED/GCSF128.145F4GCSF24.0IE = ifosfamide, etoposideCED = cyclophosphamide, etoposide, dexamethasone A.R. Shustov: I have a consultancy relationship with and have received research funding from Seattle Genetics, Inc. I have also received honoraria from Millennium. J.D. Rosenblatt: Seattle Genetics, Inc. has provided research support to my institution. D.A. Kennedy: I am an employee of and have equity ownership in Seattle Genetics, Inc. M. Fanale: I have acted as a consultant and served on Advisory Board for Seattle Genetics, Inc. I have received honoraria and travel expenses from Seattle Genetics, Inc. Seattle Genetics, Inc. has also provided research funding to my institution