Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory waldenström macroglobulinemia

Irene M. Ghobrial, Morie Gertz, Betsy LaPlant, John Camoriano, Suzanne Hayman, Martha Lacy, Stacey Chuma, Brianna Harris, Renee Leduc, Meghan Rourke, Stephen M. Ansell, Daniel DeAngelo, Angela Dispenzieri, Leif Bergsagel, Craig Reeder, Kenneth C. Anderson, Paul G. Richardson, Steven P. Treon, Thomas E. Witzig

Research output: Contribution to journalArticlepeer-review

111 Scopus citations


Purpose: The phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR) signal transduction pathway controls cell proliferation and survival. Everolimus is an oral agent targeting raptor mTOR (mTORC1). The trial's goal was to determine the antitumor activity and safety of single-agent everolimus in patients with relapsed/refractory Waldenström macroglobulinemia (WM). Patients and Methods: Eligible patients had measurable disease (immunoglobulin M monoclonal protein > 1,000 mg/dL with > 10% marrow involvement or nodal masses > 2 cm), a platelet count more than 75,000 × 106/L, a neutrophil count more than 1,000 × 106/L, and a creatinine and bilirubin less than 2 x the laboratory upper limit of normal. Patients received everolimus 10 mg orally daily and were evaluated monthly. Tumor response was assessed after cycles 2 and 6 and then every three cycles until progression. Results: Fifty patients were treated. The median age was 63 years (range, 43 to 85 years). The overall response rate (complete response plus partial remission [PR] plus minimal response [MR]) was 70% (95% CI, 55% to 82%), with a PR of 42% and 28% MR. The median duration of response and median progression-free survival (PFS) have not been reached. The estimated PFS at 6 and 12 months is 75% (95% CI, 64% to 89%) and 62% (95% CI, 48% to 80%), respectively. Grade 3 or higher related toxicities were observed in 56% of patients. The most common were hematologic toxicities with cytopenias. Pulmonary toxicity occurred in 10% of patients. Dose reductions due to toxicity occurred in 52% of patients. Conclusion: Everolimus has high single-agent activity with an overall response rate of 70% and manageable toxicity in patients with relapsed WM and offers a potential new therapeutic strategy for this patient group.

Original languageEnglish (US)
Pages (from-to)1408-1414
Number of pages7
JournalJournal of Clinical Oncology
Issue number8
StatePublished - Mar 10 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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