Alemtuzumab in B-Cell Prolymphoytic Leukemia (B-PLL) and Richter’s Transformation.

Alemtuzumab is the standard therapy for treatment of patients with relapsed/refractory B-CLL. Significant responses have also been documented in the front-line CLL setting, and as well as in first-line therapy of patients with T-PLL, a population with an exceptionally poor prognosis and few available therapeutic options. Limited data available on the therapeutic benefit of alemtuzumab in other aggressive lymphomas such as B-PLL, which is rare, with a heterogeneous clinical course, and often chemoresistant, as well as CLL with Richter’s transformation, which is also characterized by a poor clinical outcome. Here, we present data on safety and efficacy of alemtuzumab in 6 patients with B-PLL, and 2 cases of B-CLL with Richter’s transformation, both of which developed into DLBCL; one B-CLL case was atypical due to negative CD5 expression (CD19+, CD5−, CD23−). Median age for all 8 patients was 62 years (range, 58–72 years), 5 were male, and all had received a median of 3.5 prior therapies (range, 0–11). Two patients were Rai stage II and III, respectively, and 4 had Rai stage IV disease. At baseline, 3 of the 6 patients with B-PLL had poor performance status, as evidenced by exceptionally high leukocyte counts with clinical signs of hyperleukocytosis and fever of unclear origin. IV alemtuzumab 30 mg was administered according to guidelines (3 times a week, 12 weeks scheduled), but in the majority of cases, dosing was individualized. The median duration of therapy was 4.5 weeks (range, 1–12 weeks), and the median dose was 348 mg (range, 3–793 mg). Therapeutic response was determined according to NCI-WG criteria. In the 2 of 3 patients with poor PS at initiation of therapy an objective response could not be determined due to an early death (septicemia with staphylococcus); 1 patient died prior to achieving a full response due to a suspected apoplectic insult, and another patient died due to progressive disease, shortly after starting alemtuzumab. However, 2 (33%) patients with B-PLL achieved stable disease, lasting 7 months in both cases. Both patients gained a clear clinical benefit from treatment with alemtuzumab as evidenced by CR and PR in peripheral blood, individually, and transfusion independence in both patients. These 2 patients appeared to have favourable disease characteristics, as has been described by other investigators (Leukemia & Lymphoma1999; 33:169), and were diagnosed 9 and 11 years before alemtuzumab, respectively. In the 6 B-PLL patients, overall survival (OS) after start of alemtuzumab therapy was very heterogeneous (0.1; 0.2; 0.3; 1; 27+; 28 months), with a longer OS in the 2 patients with SD. In the 2 patients with B-CLL/Richters’s syndrome (as multifocal DLBCL), PD was observed in one after 2 months on alemtuzumab (survival 15 months). The patient with atypical features was receiving alemtuzumab as an 8 th line of therapy and achieved a PR lasting for 13 months (OS 31+ months). In summary, we are adding evidence of therapeutic efficacy of alemtuzumab in a subset of patients with rare, chemotherapy refractory B-lymphoproliferative diseases.