title: Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study.
abstract: OBJECTIVE
  Although dose-intensive strategies or high-dose therapy induction followed by autologous stem-cell transplantation have improved the outcome for patients with mantle-cell lymphoma (MCL), most eventually relapse and subsequently respond poorly to additional therapy. Bortezomib (in the United States) and temsirolimus (in Europe) are currently the only two treatments approved for relapsed disease. Lenalidomide is an immunomodulatory agent with proven tumoricidal and antiproliferative activity in MCL. The MCL-001 (EMERGE) trial is a global, multicenter phase II study examining the safety and efficacy of lenalidomide in patients who had relapsed or were refractory to bortezomib.
  
  
  METHODS
  Lenalidomide 25 mg orally was administered on days 1 through 21 every 28 days until disease progression or intolerance. Primary end points were overall response rate (ORR) and duration of response (DOR); secondary end points included complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety.
  
  
  RESULTS
  In all, 134 patients were enrolled with a median age of 67 years and a median of four prior therapies (range, two to 10 prior therapies). The ORR was 28% (7.5% CR/CR unconfirmed) with rapid time to response (median, 2.2 months) and a median DOR of 16.6 months (95% CI, 7.7 to 26.7 months). Median PFS was 4.0 months (95% CI, 3.6 to 5.6 months), and median OS was 19.0 months (95% CI, 12.5 to 23.9 months). The most common grade 3 to 4 adverse events were neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (8%), and fatigue (7%).
  
  
  CONCLUSIONS
  The MCL-001 study demonstrated durable efficacy of lenalidomide with a predictable safety profile in heavily pretreated patients with MCL who had all relapsed or progressed after or were refractory to bortezomib.
authors.affiliation: Andre Goy, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack; Lei Zhang, Sherri Cicero, and Tommy Fu, Celgene, Summit, NJ; Rajni Sinha, Emory University Winship Cancer Institute, Atlanta, GA; Michael E. Williams, University of Virginia Health System, Charlottesville, VA; Sevgi Kalayoglu Besisik, Istanbul University Faculty of Medicine, Istanbul, Turkey; Johannes Drach, Medical University of Vienna, Vienna, Austria; Radhakrishnan Ramchandren, Karmanos Cancer Institute, Detroit, MI; and Thomas E. Witzig, Mayo Clinic, Rochester, MN.
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: Rajni
authors.initials: R
authors.lastname: Sinha
authors.forename: Michael E
authors.initials: ME
authors.lastname: Williams
authors.forename: Sevgi
authors.initials: S
authors.lastname: Kalayoglu Besisik
authors.forename: Johannes
authors.initials: J
authors.lastname: Drach
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Ramchandren
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Sherri
authors.initials: S
authors.lastname: Cicero
authors.forename: Tommy
authors.initials: T
authors.lastname: Fu
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide