The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL Cells into the circulation

Clive S. Zent, Betsy R. LaPlant, Patrick B. Johnston, Timothy G. Call, Thomas M. Habermann, Ivana N. Micallef, Thomas E. Witzig

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

BACKGROUND: Patients with recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) often have chemotherapy-resistant disease, resulting in poor prognosis. The aim of this study was to learn if inhibition of the mammalian target of rapamycin (mTOR) would produce tumor responses. METHODS: This was a phase 2 study of oral single-agent everolimus (10 mg/day) for recurrent/refractory indolent lymphoid malignancies including CLL. RESULTS: Four of 22 patients with CLL (18%; 95% confidence interval, 5%-40%) achieved a partial remission to therapy. An unanticipated finding in this study was an increase in absolute lymphocyte count (ALC) associated with a decrease in lymphadenopathy in 8 (36%) patients. ALC increased a median of 4.8-fold (range, 1.9- to 25.1-fold), and the clinically measurable lymphadenopathy decreased a median of 75.5% (range, 38%-93%) compared with baseline measurements. CONCLUSIONS: Everolimus has modest antitumor activity against CLL and can mobilize malignant cells from nodal masses into the peripheral circulation in a subset of CLL patients. Because CLL cells in lymphatic tissue and bone marrow can be more resistant to therapy than circulating CLL cells, the ability of everolimus to mobilize CLL cells into the circulation could be used in combination therapeutic regimens.

Original languageEnglish (US)
Pages (from-to)2201-2207
Number of pages7
JournalCancer
Volume116
Issue number9
DOIs
StatePublished - May 1 2010

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Keywords

  • Chronic lymphocytic leukemia/small lymphocytic lymphoma
  • Everolimus
  • Inhibitor
  • Mobilization
  • Rapamycins
  • mTOR

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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