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.
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.
Authors: Steven P Treon; Andrew R Branagan; Leukothea Ioakimidis; Jacob D Soumerai; Christopher J Patterson; Barry Turnbull; Parveen Wasi; Christos Emmanouilides; Stanley R Frankel; Andrew Lister; Pierre Morel; Jeffrey Matous; Stephanie A Gregory; Eva Kimby Journal: Blood Date: 2008-11-17 Impact factor: 22.113
Authors: Morie A Gertz; Rafat Abonour; Leonard T Heffner; Philip R Greipp; Hajime Uno; S V Rajkumar Journal: Br J Haematol Date: 2009-09-14 Impact factor: 6.998
Authors: Steven P Treon; Jacob D Soumerai; Zachary R Hunter; Christopher J Patterson; Leukothea Ioakimidis; Brad Kahl; Michael Boxer Journal: Blood Date: 2011-05-12 Impact factor: 22.113
Authors: Jorge J Castillo; Edward N Libby; Stephen M Ansell; M Lia Palomba; Kirsten Meid; Catherine A Flynn; Carly Leventoff; Christopher B Hergott; Tomasz Sewastianik; Elizabeth A Morgan; Ruben Carrasco; Jonathan R Fromm; Guang Yang; Zachary Hunter; Steven P Treon Journal: Blood Adv Date: 2020-10-27
Authors: Roneil G Malkani; Martin Tallman; Numa Gottardi-Littell; William Karpus; Laura Marszalek; Daina Variakojis; Bruce Kaden; Matthew Walker; Robert M Levy; Jeffrey J Raizer Journal: J Neurooncol Date: 2009-07-18 Impact factor: 4.130
Authors: Aldo M Roccaro; Irene M Ghobrial; Simona Blotta; Steven P Treon; Michele Malagola; Kenneth C Anderson; Paul G Richardson; Domenico Russo Journal: Biologics Date: 2008-09