Infectious Complications in Asian Patients Treated with Alemtuzumab: Results From a Multicenter Study.
Authors: Kim Seok Jin , Reksodiputro Ary Harryanto , Cheng Ann-Lii , Intragumtornchai Tanin , Issaragrisil Surapol , Moon Joon Ho , Kim Jin Seok , Lee Je-Jung , Won Jong Ho , Kim Won Seog , Kwong Yok Lam 
Published: October 2019

Abstract
Abstract 5009

Introduction
Alemtuzumab is a monoclonal humanized antibody reactive with CD52 antigen expressed in indolent B-cell non-Hodgkin lymphomas and variably expressed in high grade B- and T-cell lymphomas. Thus, alemtuzumab has been used as a treatment for these lymphomas. Alemtuzumab has also been used for the prevention of graft-versus-host disease. However, alemtuzumab binds to 95% of normal lymphocytes resulting in long-lasting depletion of B- and T-lymphocytes. This prolonged suppression of immunity could influence the occurrences of opportunistic infections. Based on the experiences of infections associated with the use of alemtuzumab, recently the recommendations for prophylaxis against infectious complications were suggested. However, the majority of data used to establish this guideline was from the results of Western countries. Considering the prevalence of infection can be different from Asian countries to Western countries, the effective prophylaxis guideline appropriate for Asian patients should be required. Thus, we performed a multinational retrospective study about the infectious complications among Asian patients who received alemtuzumab.

Patients and methods
We reviewed the medical records of patients who were treated with alemtuzumab. The infectious complications associated with alemtuzumab were defined as any episodes of infections occurred in patients who received alemtuzumab.

Results
162 patients were assembled from 10 institutes of 5 Asian countries: Korea (5 hospitals), Hong Kong (1 hospital), Thailand (2 hospitals), Indonesia (1 hospital), and Taiwan (1 hospital). The median age was 47 years (range 11-79years), and the Korean (n = 103) and Chinese (n = 43) accounted for 90.1% of the study population. The primary disorders of patients were as follows: T-cell lymphomas (n = 93, 57.4%), B-cell lymphomas (n = 30, 18.5%), Myeloid leukemia/MDS (n = 25, 15.4%), Aplastic anemia (n = 10, 6.2%), and Benign disorder (n = 4, 2.5%). Alemtuzumab was used as frontline and salvage treatments for lymphoid malignancy (n = 120, 74.1%), and as conditioning regimen for allogeneic stem cell transplantation (n = 42). Alemtuzumab was administered as a single agent or combined with other chemotherapeutic agents. The infection prophylaxis was done according to the each institute's policy. The bacterial infections were the most common infectious complications (n = 80, 49.4%), and the median time interval between the start of alemtuzumab and the onset of bacterial infections was 2.20 months (95% confidence interval: 1.14-3.26 months). However, considering the majority of cases received intensive chemotherapy combined with alemtuzumab, this frequency of bacterial infections might be influenced by other chemotherapeutic agents. Thirty-two patients experienced fungal infections including aspergillosis and candidiasis (19.8%, median time interval 2.83 months). Fugal infections were more common when alemtuzumab was used with other chemotherapeutic agents than as a single agent. Cytomegalovirus (CMV) accounted for 40.1% of infectious complications while CMV antigenemia was more frequent than CMV disease (n = 52 versus n = 13). Vanganciclovir as well as valacyclovir prophylaxis did not significantly reduce the occurrence of CMV infections. Herpes zoster was documented in 25 patients (15.4%) and the median time interval was 6.40 months (95% confidence interval: 1.06-11.74 months). The past history of herpes zoster was not related with the occurrence of zoster after alemtuzumab was used. Tuberculosis and hepatitis B were found in 15 and 4 patients, respectively. The past history of tuberculosis and hepatitis B carrier did not affect the occurrence of tuberculosis and hepatitis B. The number of previous treatments before alemtuzumab, and the purpose of alemtuzumab such as salvage treatment and conditioning for transplantation were not significantly associated with the occurrence of infectious complications.

Conclusion
The incidence and clinical features of infectious complications associated with alemtuzumab in Asian patients were comparable to the data from Western countries. Considering a substantial number of infectious complications associated with virus, more effective prophylaxis against viral infections should be considered.

Disclosures
No relevant conflicts of interest to declare.