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D Lu, W R Gillespie, S Girish, P Agarwal, C Li, J Hirata, Y-W Chu, M Kagedal, L Leon, V Maiya, J Y Jin
Polatuzumab vedotin, an antibody-drug conjugate containing monomethyl auristatin E, was associated with an incidence of grade ≥2 peripheral neuropathy (PN) of 55-72% in patients with indolent non-Hodgkin lymphoma in a phase II study, when dosed 1.8-2.4 mg/kg every 3 weeks until progression or for a maximum of 17 cycles. To quantify the correlation of conjugate exposure and treatment duration with PN risk, a time-to-event model was developed using data from phase I and II studies. The model suggested that PN risk increased with conjugate exposure and treatment cycles, and a trend for increased risk with body weight and albumin concentration...
June 2017: CPT: Pharmacometrics & Systems Pharmacology
Michele Merli, Andrea Ferrario, Margherita Maffioli, Cecilia Olivares, Alessandra Stasia, Luca Arcaini, Francesco Passamonti
INTRODUCTION: Brentuximab vedotin (BV) is a potent anti-CD30 antibody drug conjugate (ADC) that has been approved in relapsed or refractory Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT) and anaplastic large-cell lymphoma (ALCL). Beyond these consolidated indications, BV has been tested in a number of different settings with promising results, leading for example to the recent approval as a consolidation after ASCT in high-risk HL patients. AREAS COVERED: Main emerging areas of clinical investigation of BV include the use as a single-agent or in combination with bendamustine in first-salvage therapy of HL (bridge to ASCT), in the frontline setting in combination with AVD chemotherapy in HL and with CHP in ALCL, in relapsed or refractory cutaneous T-cell lymphomas and finally in diffuse large B-cell lymphomas (DLBCL) expressing CD30...
August 2016: Expert Review of Hematology
Amitkumar Mehta, Andres Forero-Torres
Rituximab, a monoclonal antibody (MAb) against CD20, was the first MAb approved by the US Food and Drug Administration (FDA) for treatment of B cell non-Hodgkin lymphoma (B-NHL). Conjugating toxins to MAb was a technical challenge; however, with improvements in linker technology, immunoconjugates were constructed and revolutionized cancer treatment. Gemtuzumab ozogamicin was the first antibody drug conjugate (ADC) approved by the FDA. Because of the success of brentuximab vedotin and ado-trastuzumab emtansine in treating Hodgkin lymphoma (HL) and HER2-positive breast cancer, respectively, newer ADCs are being investigated...
September 2015: Current Oncology Reports
Maria Corinna A Palanca-Wessels, Myron Czuczman, Gilles Salles, Sarit Assouline, Laurie H Sehn, Ian Flinn, Manish R Patel, Randeep Sangha, Anton Hagenbeek, Ranjana Advani, Herve Tilly, Olivier Casasnovas, Oliver W Press, Sreeni Yalamanchili, Robert Kahn, Randall C Dere, Dan Lu, Surai Jones, Cheryl Jones, Yu-Waye Chu, Franck Morschhauser
BACKGROUND: Patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) have an unfavourable prognosis with few treatment options. Polatuzumab vedotin is an antibody-drug conjugate containing an anti-CD79B monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the safety and clinical activity of polatuzumab vedotin in relapsed or refractory B-cell NHL and chronic lymphocytic leukaemia (CLL). METHODS: In this phase 1, multicentre, open-label study, we enrolled patients with documented NHL or CLL expected to express CD79B (confirmation of CD79B expression was not required) and for whom no suitable therapy of curative intent or higher priority existed from 13 centres...
June 2015: Lancet Oncology
Michele Merli, Andrea Ferrario, Margherita Maffioli, Luca Arcaini, Francesco Passamonti
INTRODUCTION: The advent of the anti-CD20 mAb rituximab has opened a new era in the treatment of non-Hodgkin's lymphomas (NHL), markedly altering standard treatment strategies. Moreover, the proof-of-concept that targeting a specific lymphocyte surface antigen may induce a highly effective and safe targeted killing of malignant cells has opened the door to the development of a plethora of novel mAbs directed towards different B- and T-cell-specific antigens. AREAS COVERED: This review discusses the recent available clinical data about new-generation anti-CD20 mAbs characterized by increased antibody- (obinutuzumab) or complement-dependent cyotoxicity (ofatumumab) as well as novel investigational agents targeting other lymphocyte antigens (e...
2015: Expert Opinion on Investigational Drugs
Shang-Fan Yu, Bing Zheng, MaryAnn Go, Jeff Lau, Susan Spencer, Helga Raab, Robert Soriano, Suchit Jhunjhunwala, Robert Cohen, Michele Caruso, Paul Polakis, John Flygare, Andrew G Polson
PURPOSE: We are interested in identifying mechanisms of resistance to the current generation of antibody-drug conjugates (ADC) and developing ADCs that can overcome this resistance. EXPERIMENTAL DESIGN: Pinatuzumab vedotin (anti-CD22-vc-MMAE) and polatuzumab vedotin (anti-CD79b-vc-MMAE) are ADCs that contain the microtubule inhibitor monomethyl auristatin E (MMAE) attached to the antibody by the protease-cleavable linker maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl (MC-vc-PAB)...
July 15, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
(no author information available yet)
No abstract text is available yet for this article.
August 2014: Clinical Advances in Hematology & Oncology: H&O
M Pfeifer, B Zheng, T Erdmann, H Koeppen, R McCord, M Grau, A Staiger, A Chai, T Sandmann, H Madle, B Dörken, Y-W Chu, A I Chen, D Lebovic, G A Salles, M S Czuczman, M C Palanca-Wessels, O W Press, R Advani, F Morschhauser, B D Cheson, P Lenz, G Ott, A G Polson, K E Mundt, G Lenz
Antibody drug conjugates (ADCs), in which cytotoxic drugs are linked to antibodies targeting antigens on tumor cells, represent promising novel agents for the treatment of malignant lymphomas. Pinatuzumab vedotin is an anti-CD22 ADC and polatuzumab vedotin an anti-CD79B ADC that are both linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In the present study, we analyzed the activity of these agents in different molecular subtypes of diffuse large B-cell lymphoma (DLBCL) both in vitro and in early clinical trials...
July 2015: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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