Alemtuzumab in relapsed immune severe aplastic anemia: Long‐term results of a phase II study

Abstract

Immune severe aplastic anemia (SAA) is characterized by pancytopenia and immune‐mediated bone marrow destruction. SAA may be treated with hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). However, 30% of patients treated with IST relapse. We previously reported a clinical trial of alemtuzumab in which more than half of 25 relapsed SAA patients (56%) responded hematologically. Here, we present long‐term results of a total of 42 patients. Participants with SAA who had previously completed antithymocyte globulin (ATG)‐based IST, but had relapsed, were enrolled on this study. Alemtuzumab was administered intravenously (IV) (n = 28) or subcutaneously (SC) (n = 14). The primary endpoint was hematologic response at 6 months. Secondary endpoints included relapse, clonal evolution, and survival. This trial was registered at http://clinicaltrials.gov (NCT00195624). Patients were enrolled over 9 years, with median follow‐up of 6 years. Median age was 32 years, with 57% being female. At 6 months, 18 patients (43%) achieved response; 15 (54%) of those who received IV compared with 3 (21%) who received SC therapy. Six patients (14%) had durable long‐term response without need for subsequent AA‐directed therapy or HSCT at last follow‐up. Nine patients had clonal evolution, with high‐risk evolution occurring in 6. Overall survival was 67% at median follow‐up of 6 years. Prolonged iatrogenic immunosuppression was observed as long as 2 years after alemtuzumab administration. Alemtuzumab induces responses in relapsed SAA, some of which are durable long‐term. However, immunosuppression can persist for years, requiring long‐term monitoring.

A Case of Successful Allogeneic Hematopoietic Stem Cell Transplantation in a Severely Underweight Patient with Aplastic Anemia

“…Conditioning therapy consisted of the fludarabine/cyclophosphamide/alemtuzumab protocol with premedication [ 5 ]. The dosage of drugs was strictly controlled due to the patient's low BMI: alemtuzumab i/v 3 mg −8 day, 17 mg −7 day, 20 mg from −6th to −3rd day prior to transplant, fludarabine 32 mg i/v from −7 to −4 day, and cyclophosphamide 530 mg i/v −5 to −2 day (with mesna for prevention of hemorrhagic cystitis) [ 6 , 7 ].…”