title: Initial immunoglobulin M 'flare' after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemia: an Eastern Cooperative Oncology Group Study.
abstract: BACKGROUND
  The goal of the current study was to characterize the initial upsurge in immunoglobulin M (IgM) levels after treatment with rituximab in patients with Waldenstrom macroglobulinemia (WM).
  
  
  METHODS
  As part of a Phase II Eastern Cooperative Oncology Group study, 72 patients were treated with rituximab (375 mg/m(2) weekly for 4 weeks) between April 2000 and January 2002. IgM levels in these patients were measured at five separate time points so that any temporal changes that occurred could be characterized.
  
  
  RESULTS
  Of the 54 patients for whom the relevant IgM measurements were available, 29 (54%) experienced an increase in IgM levels between baseline and the first scheduled postbaseline time point. At 2 months, 13 of 22 evaluable patients (59%) continued to have elevated IgM levels, and at 4 months, elevated IgM levels persisted in 4 of 15 evaluable patients (27%). Overall, a nonlinear trend characterized by an initial increase in IgM levels followed by a decrease in these levels was observed (P < 0.0001).
  
  
  CONCLUSIONS
  Treating physicians should be aware that an IgM 'flare' may occur in up to 54% of patients treated with rituximab; however, most of these patients experience a decrease in IgM levels within 4 months after the initiation of therapy. Therefore, patients should not be discouraged from continuing to receive this potentially effective therapeutic agent, as responses to rituximab may develop slowly. Longer follow-up will reveal whether patients who experience an upsurge in IgM levels have poorer overall survival or shorter times to progression compared with patients who do not experience this IgM flare. Factors predicting an initial increase in IgM levels could not be identified.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
authors.forename: Emily
authors.initials: E
authors.lastname: Blood
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rue
authors.forename: David H
authors.initials: DH
authors.lastname: Vesole
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000069283:Rituximab; D016019:Survival Analysis; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007075:Immunoglobulin M; D000069283:Rituximab