Efficacy and Safety of Alemtuzumab in Patients with Relapsed B-Cell Chronic Lymphocytic Leukemia after Autologous Stem Cell Transplantation.

This phase II study investigated the efficacy and safety of alemtuzumab (Campath-1H), as treatment to achieve a second minimal residual disease (MRD) negative complete remission, in patients with relapsed B-cell chronic lymphocytic leukemia (B-CLL) after autologous stem cell transplantation (ASCT). Only patients who had experienced a posttransplantation MRD negative status and with a low tumour burden at relapse were eligible for the study. Eleven patients were treated. Nine patients were Binet Stage A and two patients had converted to an MRD positive status. The median time from ASCT was 36 months (range, 15–66 months). Alemtuzumab was administered as a 30 mg intravenous injection three times weekly for a maximum of 12 weeks. All patients received valacyclovir and trimethoprim/sulfamethoxazole as infection prophylaxis during therapy and 6 months after. Cytomegalovirus (CMV) reactivation was monitored weekly using a blood antigen test. Patients with Binet stage A were evaluated according to National Cancer Institute (NCI) criteria. MRD assessment was performed in complete responders and the two MRD relapses in blood and bone marrow using sensitive techniques as MRD Flow (Rawstron et al, Blood 2001, 98: 35) and nonspecific allele IgH PCR. Among nine patients assessed for disease response by NCI criteria, two (22%) achieved a partial response and five (55%) a complete remission (overall response rate [ORR], 77%). The overall median response duration was 9 months (range, 4–18+ months) and 12 months (range, 6–18+ months) for complete responders. Five patients (45%) converted to a phenotypic and molecular complete remission, with a median response duration of 6 months (range, 4–18+ months). Two patients remained in MRD negative complete remission after therapy at 18+ and 12+ months, respectively. The treatment-free median survival has not been reached for complete responders, with a median follow-up of 14 months. All patients were evaluable for toxicity. WHO grade 1–2 infusion-related reactions were observed in up to 90% of patients with the initial escalating dose. A moderate hematological toxicity was reported, except for platelets. Frequency of grade 3–4 events during therapy were as follows: 27% of anemia, 18% of neutropenia and 54% of thrombocytopenia. A delayed-onset neutropenia occured in three patients, up to 2 months after completion of treatment. Grade 2 infections were observed in six patients (54%). Only one patient experienced a major infection. Two patients (18%) developed CMV reactivation, CMV disease was successfully prevented by treatment with oral ganciclovir, without discontinuing alemtuzumab therapy. Alemtuzumab has demonstrated activity and safety in relapsed B-CLL patients after ASCT with an ORR of 77% and an MRD negativity of 45%. However, the question of maintaining a durable MRD negative complete response remains posed.