© 2005 European Society for Medical Oncology
Original article |
Extended rituximab therapy in Waldenström's macroglobulinemia
1 Bing Program for Waldenström's Macroglobulinemia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; 2 UCLA Medical Center, Los Angeles, CA, USA; 3 Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden; 4 Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 5 Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA
* Correspondence to: Dr S. P. Treon, Bing Program for Waldenström's Macroglobulinemia, Dana Farber Cancer Institute, LG102, 44 Binney Street, Boston, MA 02115, USA. Tel: +1-617-632-2681; Fax: +1-617-632-4862; Email: steven_treon{at}dfci.harvard.edu
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/m2/week.
Methods: In an effort to increase rituximab activity in WM, an extended dose schedule employing two sets of four (375 mg/m2/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.
Key words: Waldenström's macroglobulinemia, lymphoplasmacytic lymphoma, rituximab, CD46, CD55, CD59
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