title: Lenalidomide and rituximab in Waldenstrom's macroglobulinemia.
abstract: OBJECTIVE
  Thalidomide and its more potent immunomodulatory derivative lenalidomide enhance rituximab-mediated antibody-dependent cell-mediated cytotoxicity. We therefore evaluated lenalidomide and rituximab in symptomatic Waldenstrom's macroglobulinemia (WM) patients naive to either agent.
  
  
  METHODS
  Intended therapy consisted of 48 weeks of lenalidomide (25 mg/d for 3 weeks and then 1 week off) along with rituximab (375 mg/m(2)/wk) dosed on weeks 2 to 5 and 13 to 16. Sixteen patients were enrolled, 12 of whom were previously untreated.
  
  
  RESULTS
  Unexpectedly, we observed an acute decrease in hematocrit in 13 of 16 patients (median hematocrit decrease, 4.8%), which was attributable to lenalidomide patients and which led to cessation of further enrollment on this study. Lenalidomide-related anemia was observed even at doses as low as 5 mg/d and occurred in the absence of hemolysis or other cytopenias. The overall response and major response (<50% decrease in serum IgM) rates were 50% and 25%, respectively, on an intent-to-treat basis. With a median follow-up of 31.3 months, 4 of 8 responding patients have progressed with a median time to progression of 18.9 months.
  
  
  CONCLUSIONS
  Lenalidomide produces unexpected but clinically significant acute anemia in patients with WM. In comparison with our previous study with thalidomide and rituximab in an analogous patient population, the responses achieved in WM patients with lenalidomide and rituximab appear less favorable.
authors.affiliation: Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA 02115, USA. steven_treon@dfci.harvard.edu
authors.forename: Steven P
authors.initials: SP
authors.lastname: Treon
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Soumerai
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Branagan
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Hunter
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Patterson
authors.forename: Leukothea
authors.initials: L
authors.lastname: Ioakimidis
authors.forename: Luis
authors.initials: L
authors.lastname: Chu
authors.forename: Paul
authors.initials: P
authors.lastname: Musto
authors.forename: Ari D
authors.initials: AD
authors.lastname: Baron
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Nunnink
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Kash
authors.forename: Terenig O
authors.initials: TO
authors.lastname: Terjanian
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hyman
authors.forename: Elena L
authors.initials: EL
authors.lastname: Nawfel
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharon
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D000069283:Rituximab; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013921:Thrombocytopenia / Q000139:chemically induced; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007075:Immunoglobulin M; D000069283:Rituximab; D013792:Thalidomide; D000077269:Lenalidomide