Extended rituximab therapy in Waldenström's macroglobulinemia

• Published in: Annals of oncology Vol. 16; no. 1; pp. 132 - 138
• Main Authors: TREON, S. P, EMMANOUILIDES, C, KIMBY, E, KELLIHER, A, PREFFER, F, BRANAGAN, A. R, ANDERSON, K. C, FRANKEL, S. R
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 2005
• Subjects: 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; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Biological and medical sciences; CD55 Antigens - analysis; CD55 Antigens - biosynthesis; CD59 Antigens - analysis; CD59 Antigens - biosynthesis; Drug Administration Schedule; Female; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin M - analysis; Immunoglobulinopathies; Immunohistochemistry; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medicin och hälsovetenskap; Membrane Cofactor Protein; Membrane Glycoproteins - analysis; Membrane Glycoproteins - biosynthesis; Middle Aged; Pharmacology. Drug treatments; Rituximab; Treatment Outcome; Waldenstrom Macroglobulinemia - drug therapy; Waldenstrom Macroglobulinemia - immunology; Waldenstrom Macroglobulinemia - pathology; Waldenström's macroglobulinemia; Immunopathology; lymphoplasmacytic lymphoma; Rituximab; Malignant hemopathy; Monoclonal antibody; Lymphoma; Treatment; Immunoglobulinopathy; Lymphoproliferative syndrome; Immunotherapy; Anticytokine; CD59; Waldenstrom macroglobulinemia; CD46; CD55
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdi022

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. 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. 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). 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.