Long-term follow-up of symptomatic patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia treated with the anti-CD52 monoclonal antibody alemtuzumab

Abstract

CD52 is expressed on malignant cells in lymphoplasmacytic lymphoma (LPL), including IgM-secreting Waldenström macroglobulinemia (WM). We examined the activity of alemtuzumab in 28 symptomatic LPL (27 IgM and 1 IgA) patients. The median prior number of therapies for these patients was 2 (range, 0-5) and 43% had refractory disease. Patients received alemtuzumab at 30 mg IV 3 times weekly for up to 12 weeks after test dosing, and also received hydrocortisone, acyclovir, and Bactrim or equivalent prophylaxis. Patients had a complete response (n = 1), a partial response (n = 9), or a MR (n = 11) for an overall and major response rate of 75% and 36%, respectively. Median serum Ig decreased from 3510 to 1460 mg/dL (P < .001 at best response). With a median follow-up of 64 months, the median time to progression was 14.5 months. Hematologic and infectious complications, including CMV reactivation, were more common in previously treated patients and were indirectly associated with 3 deaths. Long-term follow-up revealed late-onset autoimmune thrombocytopenia (AITP) in 4 patients at a median of 13.6 months after therapy, which contributed to 1 death. Alemtuzumab is an active therapy in patients with LPL, but short- and long-term toxicities need to be carefully weighed against other available treatment options. Late AITP is a newly recognized complication of alemtuzumab in this patient population. This study is registered at www.clinicaltrials.gov as NCT00142181.

Figures

Figure 1

Relative changes in serum Ig levels for 26 evaluable LPL patients at best response after treatment with alemtuzumab.

Figure 2

TTP in 28 LPL patients treated with alemtuzumab.

Figure 3

Median absolute peripheral blood CD4+, CD8+, CD16+56+, CD19+, and monocytic cell levels after alemtuzumab therapy. Cell levels were measured at baseline (0), 6 and 12 weeks (W), and 6-24 months (M) after alemtuzumab therapy. The number of patients evaluated at each time point were as follows: 0, n = 26; 6W, n = 18; 12W, n = 22; 6M, n = 16; 9M, n = 17; 12M, n = 13; 15M, n = 10; 18M, n = 11; and 24M, n = 8.