Long-term follow-up of patients with lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia) who were treated with alemtuzumab.

Abstract

8109 Background: CD52 is widely expressed on BM lymphoplasmacytic cells and growth supporting mast cells in lymphoplasmacytic lymphoma (LPL). We therefore examined the activity of alemtuzumab in LPL. Methods: 28 patients with LPL (27 IgM; 1 IgA) were enrolled. Baseline characteristics: Median age 60 years; BM involvement 30%; serum Ig 3,510 mg/dL; hematocrit 35%. Median prior therapies was 2 (range 0-5), and 12/28 (43%) had refractory disease. Patients received 3 test doses of alemtuzumab (3, 10, 30 mg IV), then 30 mg IV TIW for up to 12 weeks. Patients received acyclovir and bactrim or equivalent prophylaxis. Results: Responses: CR (n=1); PR (n=9); MR (n=11) for an overall and major RR of 75% and 36%, respectively. Median serum Ig decreased from 3,510 to 1,460 mg/dL; p<0.001 at best response. With a median follow-up of 55 months, the median TTP is 16 months. Hematological toxicities were common among previously treated, but not untreated patients. Grade ≥ 3 toxicities included neutropenia 54%; thrombocytopenia 25%; anemia 11%; rash 11%; infection 7%. CMV reactivation and infection were common among previously treated patients, and etiological for one death. Two other patients succumbed on study, one related in part to complications of drug therapy directed at CMV infection, and another prompted by treatment-related thrombocytopenia in a patient with Von Willebrand's. Long term follow-up revealed late-onset idiopathic thrombocytopenia in 4 patients at a median of 13.6 (range 3.9-24.6 months) following therapy. An important and unexpected finding was the restoration of peripheral blood (PB) CD19+ B lymphocytes, and IgG levels following alemtuzumab therapy (p<0.01 and 0.06, respectively). Conclusions: Alemtuzumab is highly active in patients with LPL. Toxicity was common, particularly among previously treated patients. ITP was observed as a late treatment manifestation. Recovery of CD19+ cells and serum IgG levels suggests that a CD52+ population may be responsible for the PB B-cell lymphopenia and IgG hypogammaglobulinemia commonly observed in LPL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen Idec, Celgene, Genentech, Millennium Biogen Idec, Celgene, Genentech, Millennium Celgene, Millennium