Extended rituximab therapy in Waldenström's macroglobulinemia.
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.
Treon
S P
SP
Bing Program for Waldenström's Macroglobulinemia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. steven_treon@dfci.harvard.edu
Emmanouilides
C
C
Kimby
E
E
Kelliher
A
A
Preffer
F
F
Branagan
A R
AR
Anderson
K C
KC
Frankel
S R
SR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018958:CD55 Antigens / Q000032:analysis / Q000096:biosynthesis; D018957:CD59 Antigens / Q000032:analysis / Q000096:biosynthesis; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D000970:Antineoplastic Agents; C497857:CD46 protein, human; D018958:CD55 Antigens; D018957:CD59 Antigens; D007075:Immunoglobulin M; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D000069283:Rituximab