title: Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium.
abstract: OBJECTIVE
  Despite high initial remission rates, most lymphomas relapse and require further therapy. The mammalian target of rapamycin (mTOR) pathway is a validated target in mantle cell lymphoma, but has not been extensively evaluated in other lymphomas.
  
  
  METHODS
  We performed a phase II trial of single-agent temsirolimus 25-mg weekly in patients with relapsed aggressive and indolent lymphomas. The primary objective was overall and complete response rate. Patients were stratified by histology: group A (diffuse large B-cell lymphoma, transformed follicular lymphoma), group B (follicular lymphoma), and group C (chronic lymphocytic leukemia/small lymphocytic lymphoma, and other indolent lymphomas).
  
  
  RESULTS
  Eighty-nine patients were treated, with outcome strongly dependent on histology. Group A had an overall and complete response rate of 28.1% and 12.5%, respectively, and median progression-free survival (PFS) of 2.6 months and median overall survival (OS) of 7.2 months. Group B had overall and complete response rates of 53.8% and 25.6%, respectively, and median PFS of 12.7 months; median OS has not yet been reached. Group C had a partial response rate of 11% with no complete responders. Toxicity was mainly mild and/or reversible myelosuppression and mucositis; however, four patients developed pneumonitis.
  
  
  CONCLUSIONS
  Single-agent temsirolimus has significant activity in both diffuse large B-cell lymphoma and follicular lymphoma, although the durability of responses and PFS are longer for patients with follicular lymphoma. This is the first report of substantial activity of temsirolimus in lymphomas other than mantle cell lymphoma, and supports further evaluation of mTOR as a target in these diseases.
authors.affiliation: The University of Chicago, Chicago, IL 60637, USA. smsmith@medicine.bsd.uchicago.edu
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
authors.forename: Theodore
authors.initials: T
authors.lastname: Karrison
authors.forename: Janet
authors.initials: J
authors.lastname: Dancey
authors.forename: Peter
authors.initials: P
authors.lastname: McLaughlin
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.forename: Scott
authors.initials: S
authors.lastname: Smith
authors.forename: Patrick
authors.initials: P
authors.lastname: Stiff
authors.forename: Eric
authors.initials: E
authors.lastname: Lester
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Modi
authors.forename: L Austin
authors.initials: LA
authors.lastname: Doyle
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D002641:Chicago; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D008224:Lymphoma, Follicular / Q000188:drug therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D011014:Pneumonia / Q000139:chemically induced; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism*; D012074:Remission Induction; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus