{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:39:23Z","timestamp":1791257963665,"version":"4.1.0"},"reference-count":48,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2010,3,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>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 Waldenstr\u00f6m macroglobulinemia (WM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>\n                      Eligible patients had measurable disease (immunoglobulin M monoclonal protein &gt; 1,000 mg\/dL with &gt; 10% marrow involvement or nodal masses &gt; 2 cm), a platelet count more than 75,000 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \/L, a neutrophil count more than 1,000 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      \/L, and a creatinine and bilirubin less than 2 \u00d7 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.2009.24.0994","type":"journal-article","created":{"date-parts":[[2010,2,8]],"date-time":"2010-02-08T21:59:05Z","timestamp":1265666345000},"page":"1408-1414","source":"Crossref","is-referenced-by-count":117,"title":["Phase II Trial of the Oral Mammalian Target of Rapamycin Inhibitor Everolimus in Relapsed or Refractory Waldenstr\u00f6m Macroglobulinemia"],"prefix":"10.1200","volume":"28","author":[{"given":"Irene M.","family":"Ghobrial","sequence":"first","affiliation":[{"name":"From the Dana Farber Cancer 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