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Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma.
Vogl, Dan T; Dingli, David; Cornell, Robert Frank; Huff, Carol Ann; Jagannath, Sundar; Bhutani, Divaya; Zonder, Jeffrey; Baz, Rachid; Nooka, Ajay; Richter, Joshua; Cole, Craig; Vij, Ravi; Jakubowiak, Andrzej; Abonour, Rafat; Schiller, Gary; Parker, Terri L; Costa, Luciano J; Kaminetzky, David; Hoffman, James E; Yee, Andrew J; Chari, Ajai; Siegel, David; Fonseca, Rafael; Van Wier, Scott; Ahmann, Gregory; Lopez, Ilsel; Kauffman, Michael; Shacham, Sharon; Saint-Martin, Jean-Richard; Picklesimer, Carla D; Choe-Juliak, Cassandra; Stewart, A Keith.
Afiliação
  • Vogl DT; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Dingli D; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Cornell RF; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Huff CA; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Jagannath S; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Bhutani D; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Zonder J; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Baz R; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Nooka A; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Richter J; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Cole C; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Vij R; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Jakubowiak A; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Abonour R; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Schiller G; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Parker TL; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Costa LJ; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Kaminetzky D; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Hoffman JE; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Yee AJ; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Chari A; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Siegel D; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Fonseca R; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Van Wier S; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Ahmann G; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Lopez I; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Kauffman M; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Shacham S; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Saint-Martin JR; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Picklesimer CD; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Choe-Juliak C; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
  • Stewart AK; Dan T. Vogl, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; David Dingli, Mayo Clinic, Rochester, MN; Robert Frank Cornell, Vanderbilt University Medical Center, Nashville, TN; Carol Ann Huff, Johns Hopkins University, Baltimore, MD; Sundar Jaganna
J Clin Oncol ; 36(9): 859-866, 2018 03 20.
Article em En | MEDLINE | ID: mdl-29381435
ABSTRACT
Purpose Selinexor, a first-in-class, oral, selective exportin 1 (XPO1) inhibitor, induces apoptosis in cancer cells through nuclear retention of tumor suppressor proteins and the glucocorticoid receptor, along with inhibition of translation of oncoprotein mRNAs. We studied selinexor in combination with low-dose dexamethasone in patients with multiple myeloma refractory to the most active available agents. Patients and Methods This phase II trial evaluated selinexor 80 mg and dexamethasone 20 mg, both orally and twice weekly, in patients with myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide (quad-refractory disease), with a subset also refractory to an anti-CD38 antibody (penta-refractory disease). The primary end point was overall response rate (ORR). Results Of 79 patients, 48 had quad-refractory and 31 had penta-refractory myeloma. Patients had received a median of seven prior regimens. The ORR was 21% and was similar for patients with quad-refractory (21%) and penta-refractory (20%) disease. Among patients with high-risk cytogenetics, including t(4;14), t(14;16), and del(17p), the ORR was 35% (six of 17 patients). The median duration of response was 5 months, and 65% of responding patients were alive at 12 months. The most common grade ≥ 3 adverse events were thrombocytopenia (59%), anemia (28%), neutropenia (23%), hyponatremia (22%), leukopenia (15%), and fatigue (15%). Dose interruptions for adverse events occurred in 41 patients (52%), dose reductions occurred in 29 patients (37%), and treatment discontinuation occurred in 14 patients (18%). Conclusion The combination of selinexor and dexamethasone has an ORR of 21% in patients with heavily pretreated, refractory myeloma with limited therapeutic options.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Receptores Citoplasmáticos e Nucleares / Carioferinas / Mieloma Múltiplo Tipo de estudo: Clinical_trials Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Receptores Citoplasmáticos e Nucleares / Carioferinas / Mieloma Múltiplo Tipo de estudo: Clinical_trials Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article