Alemtuzumab for Treatment-Naïve and Relapsed-Refractory Severe Acquired Aplastic Anemia

Introduction: Antithymocyte globulin (ATG) + cyclosporine is effective in restoring hematopoiesis in severe aplastic anemia (SAA). Horse ATG appears to be better than rabbit ATG. Limitations to ATG use in developing countries include cost, horse ATG availability and the reduced number of hospital beds in hematology treatment centers are frequent. Alemtuzumab, a humanized anti-CD52 mAb, might be active in SAA because of its lymphocytotoxic properties. Subcutaneous alemtuzumab have about ORR 66% and is available in Brazil through a compassionate use program. Methods: Fourteen consecutive transplant-ineligible SAA patients were treated. Alemtuzumab was administered subcutaneously in a single at escalating dose of 3-10-30-(30)-(30) mg. Premedication included intravenous steroid, antihistamine and oral acetaminophen. The total dose was 103 mg for 14 patients, and 43 mg for one elderly frail patient. Low dose (1 mg/kg) oral cyclosporine was started on day 7, and then adjusted according to plasma levels (targeting 100-200 ng/ml using a monoclonal assay) at the time of immune reconstitution. Anti-infectious prophylaxis included oral acyclovir and trimethoprim-sulphametoxazole, weekly monitoring of CMV viraemia, and oral quinolone and fluconazole in case of severe neutropenia (<0.5x 10⁹/L). Results: Fifteen SAA patients were treated. Primary outcome was hematologic response at 3months. Median age was 48 years, and 9 (60%) were male. Eight patients were treatment-naive, and 7 (46%) were relapsed-refractory. Eight patients presented PNH clone at the initial investigation, with a size clone between 0.001 to 55 in granulocytes and 0.001 to 98 in monocytes. Median time between SAA diagnosis and alemtuzumab treatment was 9 months (range 1-300). No treatment-related serious adverse events due were observed. Infectious complications were rare. The overall response rate was 66% (60% with PR, 40% CR). The median follow-up is about 29 months (range 5-69). The 3-year overall survival was 73%. Conclusion: The combination of subcutaneous alemtuzumab + cyclosporine appears to be effective and sufficiently safe in transplant-ineligible SAA patients. Moreover, it is feasible in a scenario of limited resources and low accessibility to ATG.