A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma

Patrick B. Johnston, David J. Inwards, Joseph P. Colgan, Betsy R. Laplant, Brian F. Kabat, Thomas M. Habermann, Ivana N. Micallef, Luis F. Porrata, Stephen M. Ansell, Craig B. Reeder, Vivek Roy, Thomas E. Witzig

Research output: Contribution to journalArticle

Abstract

Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin lymphoma (HL). The goal of this trial was to learn the antitumor activity and toxicity of everolimus in patients with relapsed/refractory HL. Patients were eligible if they had measurable disease, a platelet count >75,000, and an absolute neutrophil count >1,000. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Response was assessed after two and six cycles and then every three cycles until progression. Patients could remain on drug until progression or toxicity. Nineteen patients were enrolled. Median age was 37 years (range, 27-68). Patients had received a median of six prior therapies (range, 3-14) and 84% had undergone prior autologous stem cell transplant. The ORR was 47% (95% CI: 24-71%) with eight patients achieving a PR and one patient achieving a CR. The median TTP was 7.2 months. Four responders remained progression free at 12 months. Patients received a median of seven cycles of therapy. Of the 19 patients, one remains on therapy at 36 months; the others went off study because of progressive disease (16), toxicity (1), and death from infection (1). Four patients experienced a Grade 3 or higher pulmonary toxicity. Everolimus has single-agent activity in relapsed/refractory HL and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant.

Original languageEnglish (US)
Pages (from-to)320-324
Number of pages5
JournalAmerican Journal of Hematology
Volume85
Issue number5
DOIs
StatePublished - May 2010

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Hodgkin Disease
Everolimus
Phosphatidylinositol 3-Kinase
Raptors
Sirolimus
Platelet Count
Antineoplastic Agents
Signal Transduction
Neutrophils
Stem Cells
Therapeutics
Transplants
Lung

ASJC Scopus subject areas

  • Hematology

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A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. / Johnston, Patrick B.; Inwards, David J.; Colgan, Joseph P.; Laplant, Betsy R.; Kabat, Brian F.; Habermann, Thomas M.; Micallef, Ivana N.; Porrata, Luis F.; Ansell, Stephen M.; Reeder, Craig B.; Roy, Vivek; Witzig, Thomas E.

In: American Journal of Hematology, Vol. 85, No. 5, 05.2010, p. 320-324.

Research output: Contribution to journalArticle

Johnston, Patrick B. ; Inwards, David J. ; Colgan, Joseph P. ; Laplant, Betsy R. ; Kabat, Brian F. ; Habermann, Thomas M. ; Micallef, Ivana N. ; Porrata, Luis F. ; Ansell, Stephen M. ; Reeder, Craig B. ; Roy, Vivek ; Witzig, Thomas E. / A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. In: American Journal of Hematology. 2010 ; Vol. 85, No. 5. pp. 320-324.
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