Extended rituximab therapy in Waldenström's macroglobulinemia

Ann Oncol. 2005 Jan;16(1):132-8. doi: 10.1093/annonc/mdi022.


Background: Waldenström's macroglobulinemia (WM) is a CD20 expressing B-cell malignancy represented by the pathological diagnosis of IgM secreting lymphoplasmacytic lymphoma. Major response rates of 30% have been reported in most studies with standard dose rituximab, i.e. 4 weekly infusions at 375 mg/m(2)/week.

Methods: In an effort to increase rituximab activity in WM, an extended dose schedule employing two sets of four (375 mg/m(2)/week) infusions at weeks 1-4 and 12-16 was evaluated. Expression of the complement resistance antigens CD46, CD55 and CD59 was also evaluated on tumor cells pre- and post-therapy to determine impact on response.

Results: Twenty-nine patients were enrolled and 26 patients completed the intended therapy. On an intent to treat analysis, 14 (48.3%) patients achieved a partial response, and 5 (17.2%) patients achieved a minor response. Responses were observed in 18/24 (75%) patients with a serum IgM level of <6000 mg/dl, and only 1 of 5 (20%) patients with a level of >6000 mg/dl (P=0.03). The median time to best response was 17 months, and only 2 of 19 responding patients progressed with a median follow-up of 29 months. No differences in baseline expression of the complement resistance antigens CD46, CD55 and CD59 were observed among responding and non-responding patients, although post-therapy CD55 expression was higher in non-responding patients (P=0.002).

Conclusions: These data show that extended rituximab therapy is active and may lead to more major responses over standard dose rituximab in WM. WM patients with serum IgM levels of <6000 mg/dl are more likely to benefit from extended rituximab therapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD / analysis
  • Antigens, CD / biosynthesis
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • CD55 Antigens / analysis
  • CD55 Antigens / biosynthesis
  • CD59 Antigens / analysis
  • CD59 Antigens / biosynthesis
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunoglobulin M / analysis
  • Immunohistochemistry
  • Male
  • Membrane Cofactor Protein
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / biosynthesis
  • Middle Aged
  • Rituximab
  • Treatment Outcome
  • Waldenstrom Macroglobulinemia / drug therapy*
  • Waldenstrom Macroglobulinemia / immunology
  • Waldenstrom Macroglobulinemia / pathology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD
  • Antineoplastic Agents
  • CD46 protein, human
  • CD55 Antigens
  • CD59 Antigens
  • Immunoglobulin M
  • Membrane Cofactor Protein
  • Membrane Glycoproteins
  • Rituximab