Browsing by Author "Levy, Ronald"

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    Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody
    (AACR, 2017) Segal, Neil H.; Logan, Theodore F.; Hodi, F. Stephen; McDermott, David; Melero, Ignacio; Hamid, Omid; Schmidt, Henrik; Robert, Caroline; Chiarion-Sileni, Vanna; Ascierto, Paolo A.; Maio, Michele; Urba, Walter J.; Gandadhar, Tara C.; Suryawanshi, Satyendra; Neely, Jaclyn; Jure-Kunkel, Maria; Krishnan, Suba; Kohrt, Holbrook; Sznol, Mario; Levy, Ronald; Medicine, School of Medicine
    Purpose: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients with advanced solid tumors and lymphoma. Experimental Design: A total of 346 patients with advanced cancers who had progressed after standard treatment received at least one dose of urelumab in one of three dose–escalation, monotherapy studies. Urelumab was administered at doses ranging from 0.1 to 15 mg/kg. Safety analyses included treatment-related and serious adverse events (AEs), as well as treatment-related AEs leading to discontinuation and death, with a focus on liver function test abnormalities and hepatic AEs. Results: Urelumab doses between 1 and 15 mg/kg given every 3 weeks resulted in a higher frequency of treatment-related AEs than 0.1 or 0.3 mg/kg every 3 weeks. Dose was the single most important factor contributing to transaminitis development, which was more frequent and severe at doses ≥1 mg/kg. At the MTD of 0.1 mg/kg every 3 weeks, urelumab was relatively well tolerated, with fatigue (16%) and nausea (13%) being the most common treatment-related AEs, and was associated with immunologic and pharmacodynamic activity demonstrated by the induction of IFN-inducible genes and cytokines. Conclusions: Integrated evaluation of urelumab safety data showed significant transaminitis was strongly associated with doses of ≥1 mg/kg. However, urelumab 0.1 mg/kg every 3 weeks was demonstrated to be safe, with pharmacodynamic activity supporting continued clinical evaluation of this dose as monotherapy and in combination with other immuno-oncology agents.
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    The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia
    (BioMed Central, 2016-12-20) Boyiadzis, Michael; Bishop, Michael R.; Abonour, Rafat; Anderson, Kenneth C.; Ansell, Stephen M.; Avigan, David; Barbarotta, Lisa; Barrett, Austin John; Van Besien, Koen; Bergsagel, Leif; Borrello, Ivan; Brody, Joshua; Brufsky, Jill; Cairo, Mitchell; Chari, Ajai; Cohen, Adam; Cortes, Jorge; Forman, Stephen J.; Friedberg, Jonathan W.; Fuchs, Ephraim J.; Gore, Steven D.; Jagannath, Sundar; Kahl, Brad S; Kline, Justin; Kochenderfer, James N.; Kwak, Larry W.; Levy, Ronald; de Lima, Marcos; Litzow, Mark R.; Mahindra, Anuj; Miller, Jeffrey; Munshi, Nikhil C.; Orlowski, Robert Z.; Pagel, John M.; Porter, David L.; Russell, Stephen J.; Schwartz, Karl; Shipp, Margaret A.; Siegel, David; Stone, Richard M.; Tallman, Martin S.; Timmerman, John M.; Van Rhee, Frits; Waller, Edmund K.; Welsh, Ann; Werner, Michael; Wiernik, Peter H.; Dhodapkar, Madhav V.; Department of Medicine, IU School of Medicine
    Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicine’s clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves.