First Line Antiviral Therapy Significantly Improves Survival of Patients with Acute, Chronic and Smoldering ATL: a Worldwide Meta-Analysis.

Abstract 108

HTLV-I associated adult T cell leukemia/lymphoma (ATL) is an aggressive T cells malignancy, with poor prognosis due to chemotherapy resistance. Multiple small studies using zidovudine (AZT) and interferon-α (IFN) showed response in ATL patients. However, the global impact of this innovative antiviral treatment strategy on long-term survival of ATL patients in routine practice remains undetermined. We realized a worldwide meta-analysis on the use of AZT/IFN treatment. Charts of 254 ATL patients treated from 1994 to 2008 in the USA (59 patients), the UK (13 patients), Martinique (111 patients) and France metropolitaine (67 patients) were individually reviewed. Collected data included epidemiological, clinical and biological characteristics, ATL subtype, first line treatment, response to first line therapy, and overall survival. In 231 patients with available survival data, first line therapy was recorded in 207 patients only. Median age was 50 years (range 16 to 95). According to Shimoyama classification, there were 116 acute ATL, 18 chronic ATL, 11 smoldering ATL, 100 ATL lymphoma, and 9 patients with an unknown subtype. Hypercalcemia was present in 48% of patients. Five year overall survival rates were 20% for 77 patients who received chemotherapy alone, 46% for 75 patients who received first line antiviral therapy alone (p=0.012), and 12% for 55 patients who received chemotherapy followed by antiviral therapy. Response rate to first line antiviral therapy was 66%, including 35% complete remission (CR). When overall survival analysis was performed by ATL subtype, patients with acute, chronic, and smoldering ATL significantly benefited from first line antiviral therapy, whereas patients with ATL lymphoma had a better outcome with first line chemotherapy. Achievement of CR with first line antiviral therapy resulted in prolonged survival of more than 10 years in 82% of the acute ATL subgroup. Finally, first line antiviral therapy in chronic and smoldering ATL resulted in 100% overall survival at 10 years. Multivariate analysis using Cox regression showed that first line antiviral therapy significantly improves overall survival of ATL patients. In conclusion, these results confirm that treatment of ATL using AZT and IFN results in a high response and CR rates particularly in acute, chronic and smoldering ATL, but not in lymphoma, resulting in impressive prolonged survival and hence should be considered as gold standard first line therapy. Predictive factors of response are currently under investigations in order to improve prognosis of this still uncurable disease.