title: Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study.
abstract: BACKGROUND
  Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor with single-agent antitumour activity in patients with mantle cell lymphoma. We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma.
  
  
  METHODS
  In a phase 2 study, patients (aged ≥18 years) at 35 centres in the USA were given temsirolimus 25 mg/week, and rituximab 375 mg/m(2) per week for 4 weeks during the first cycle and thereafter a single dose of rituximab every other 28-day cycle. Both drugs were administered intravenously. Responding patients after six cycles could continue treatment for a total of 12 cycles, and were then observed without additional maintenance treatment. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had at least a partial response. The analyses were done on all patients who were treated. The study was registered with ClinicalTrials.gov, number NCT00109967.
  
  
  RESULTS
  71 patients with mantle cell lymphoma were enrolled and 69 were assessable and were included in the final analysis. The overall response rate (ORR) was 59% (41 of 69 patients)-13 (19%) patients had complete responses and 28 (41%) had partial responses. The ORR was 63% (30 of 48; 95% CI 47-76) for rituximab-sensitive patients, and 52% (11 of 21; 30-74) for rituximab-refractory patients. The most common treatment-related grade 3 or 4 adverse events in rituximab-sensitive and rituximab-refractory patients were thrombocytopenia (eight [17%] and eight [38%], respectively), neutropenia (ten [21%] and five [24%], respectively), fatigue (eight [17%] and two [10%], respectively), leucopenia (six [13%] and three [14%], respectively), pneumonia (five [10%] and two [10%], respectively), lymphopenia (five [10%] and two [10%], respectively), pneumonitis (four [8%] and none, respectively), oedema (four [8%] and none, respectively), dyspnoea (three [6%] and two [10%], respectively), and hypertriglyceridaemia (three [6%] and two [10%], respectively).
  
  
  CONCLUSIONS
  mTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory mantle cell lymphoma.
  
  
  BACKGROUND
  National Institutes of Health and the Predolin Foundation.
authors: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA. ansell.stephen@mayo.edu
authors: Stephen M
authors: SM
authors: Ansell
authors: Hui
authors: H
authors: Tang
authors: Paul J
authors: PJ
authors: Kurtin
authors: Patricia A
authors: PA
authors: Koenig
authors: David J
authors: DJ
authors: Inwards
authors: Keith
authors: K
authors: Shah
authors: Steven C
authors: SC
authors: Ziesmer
authors: Andrew L
authors: AL
authors: Feldman
authors: Radha
authors: R
authors: Rao
authors: Mamta
authors: M
authors: Gupta
authors: Charles
authors: C
authors: Erlichman
authors: Thomas E
authors: TE
authors: Witzig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D000069283:Rituximab; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; C401859:temsirolimus; D020123:Sirolimus