Phase 2 study of the efficacy and safety of the combination of arsenic trioxide, interferon alpha, and zidovudine in newly diagnosed chronic adult T-cell leukemia/lymphoma (ATL)

• Published in: Blood 2009-06, Vol.113 (26), p.6528-6532
• Main Authors: Kchour, Ghada, Tarhini, Mahdi, Kooshyar, Mohamad-Mehdi, El Hajj, Hiba, Wattel, Eric, Mahmoudi, Mahmoud, Hatoum, Hassan, Rahimi, Hossein, Maleki, Masoud, Rafatpanah, Houshang, Rezaee, S.A. Rahim, Yazdi, Mojtaba Tabatabaei, Shirdel, Abbas, de Thé, Hugues, Hermine, Olivier, Farid, Reza, Bazarbachi, Ali
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Arsenic Trioxide; Arsenicals - administration & dosage; Arsenicals - adverse effects; Chemical and Drug Induced Liver Injury - etiology; Drug Eruptions - etiology; Drug Synergism; Female; Gastrointestinal Diseases - chemically induced; Hematologic Diseases - chemically induced; Human T-lymphotropic virus 1 - isolation & purification; Humans; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Leukemia-Lymphoma, Adult T-Cell - drug therapy; Male; Middle Aged; Oxides - administration & dosage; Oxides - adverse effects; Proviruses - isolation & purification; Remission Induction; Viral Load; Zidovudine - administration & dosage; Zidovudine - adverse effects
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-03-211821

Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-κB activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy.