New combination therapy shows clinical promise for adult T-cell leukaemia

Adult T-cell leukaemia/lymphoma (ATL), which is a rare T-cell cancer thought to be caused by a human retrovirus, does not respond to chemotherapy and carries a dismal prognosis. Although combination therapy with the antiretroviral zidovudine (AZT) and interferon-alpha (IFN) appears promising, most patients eventually relapse, so new therapies are needed.

Arsenic trioxide (As) and IFN trigger suicide in cultured ATL cells, and the combination is therapeutically useful in some patients with an aggressive form of the disease. So, an international team of researchers, including representatives from Iran and Lebanon, conducted a prospective phase 2 clinical trial to investigate the safety and efficacy of combined AZT, IFN and As in 10 newly-diagnosed chronic ATL patients.

All patients responded quickly and positively. Seven achieved complete remission, two experienced complete remission but with circulating abnormal lymphocytes, and one experienced a partial response. Within 1 month, the proviral load had dropped significantly and the most frequent symptoms — skin rashes, itching and ulcers — had mainly disappeared. All of the patients were alive and relapse-free at an 8-month follow-up.

Most patients experienced some degree of toxicity, and had either their dose reduced or their treatment transiently stopped. The impressive response rate, however, highlights the potential of this triple therapy to treat chronic ATL. Intriguingly, the combination appears to kill selectively leukaemia-initiating cells, which fuel re-growth and relapse. However, long-term follow-up is needed to clarify whether these promising results will translate into a cure.

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