Efficacy of the oral mTORC1 inhibitor everolimus in relapsed or refractory indolent lymphoma

Nabila Bennani, Betsy R. LaPlant, Stephen Maxted Ansell, Thomas Matthew Habermann, David J. Inwards, Ivana Micallef, Patrick Bruce Johnston, Luis F. Porrata, Joseph P. Colgan, Svetomir Nenad Markovic, Grzegorz S Nowakowski, William R. Macon, Craig B. Reeder, Joseph R Mikhael, Donald W Northfelt, Irene M. Ghobrial, Thomas Elmer Witzig

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas. Eligible patients received oral everolimus 10 mg daily on a 28 day-cycle schedule. The primary endpoint was to evaluate the overall response rate (ORR) and safety of single-agent everolimus in this patient population. Fifty-five patients with indolent lymphoma were accrued. The median age was 67 years (range: 33-85) with a median of five prior therapies (range: 1-10). The ORR was 35% (19/55; 95% CI: 24-48%), with complete response unconfirmed in 4% (2/55), and partial response in 31% (17/55). The ORR was 61% (14/23) in the patients with FL. The median time to response was 2.3 months (range: 1.4-14.1), median duration of response of 11.5 months (95%-CI: 5.7-30.4), and a median progression-free survival of 7.2 months (95%-CI: 5.5-12.5). The most common toxicity was hematologic with grades 3-4 anemia, neutropenia, and thrombocytopenia documented in 15% (8/55), 22% (12/55), and 33% (18/55), respectively. There were no cases of febrile neutropenia, and eight patients discontinued therapy because of adverse events. Everolimus monotherapy is a valid therapeutic option in the relapsed and/or refractory indolent non-Hodgkin lymphoma patients and is well tolerated.

Original languageEnglish (US)
Pages (from-to)448-453
Number of pages6
JournalAmerican Journal of Hematology
Volume92
Issue number5
DOIs
StatePublished - May 1 2017

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Lymphoma
Therapeutics
Safety
Febrile Neutropenia
Everolimus
mechanistic target of rapamycin complex 1
Neutropenia
Phosphatidylinositol 3-Kinases
Thrombocytopenia
Non-Hodgkin's Lymphoma
Disease-Free Survival
Anemia
Appointments and Schedules
Clinical Trials
Population

ASJC Scopus subject areas

  • Hematology

Cite this

Efficacy of the oral mTORC1 inhibitor everolimus in relapsed or refractory indolent lymphoma. / Bennani, Nabila; LaPlant, Betsy R.; Ansell, Stephen Maxted; Habermann, Thomas Matthew; Inwards, David J.; Micallef, Ivana; Johnston, Patrick Bruce; Porrata, Luis F.; Colgan, Joseph P.; Markovic, Svetomir Nenad; Nowakowski, Grzegorz S; Macon, William R.; Reeder, Craig B.; Mikhael, Joseph R; Northfelt, Donald W; Ghobrial, Irene M.; Witzig, Thomas Elmer.

In: American Journal of Hematology, Vol. 92, No. 5, 01.05.2017, p. 448-453.

Research output: Contribution to journalArticle

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