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New drugs for therapy of AML

Leukemia volume 16, pages 306–309 (2002)Cite this article

Several novel agents have emerged recently for therapy for acute myeloid leukemia (AML). Among these are drugs that specifically bind to the surface of the acute myeloid leukemia (AML) blast such as Mylotarg (gemtuzumab ozogamicin; CMA-676), or combinations between diphtheria toxin and antibodies to the GM-CSF or IL-3 receptor. Agents have been designed to inhibit the multidrug-resistant (MDR) protein, the enzyme farnesyl transferase, the processes of angiogenesis and methylation. Lastly, a nucleoside analog, troxacitabine, has shown activity in AML and chronic myeloid leukemia (CML) in blast phase.

Gemtuzumab Gemtuzumab, a conjugate of an antibody to CD33 and the antitumor agent calicheamicin, was recently approved by the US Food and Drug Administration for treatment of adults over age 60 who have CD33-positive AML in first relapse. However, given the absence of proven successful alternatives, it is likely that the drug is being used in older patients with untreated AML and in younger patients with AML in relapse. This begs the important issue of the relative efficacies of gemcitabine and available alternatives. Two retrospective analyses have addressed this issue: one in relapsed AML and the second (described in the next paragraph) in newly diagnosed AML. In the first, Leopold et al1 compared CR rates in two groups of patients: the 128 of the 142 patients with AML in first relapse who participated in the multicenter phase II trials that led to the approval of gemtuzumab,2 and for whom cytogenetic information was available, and 128 patients treated with ara-C plus or minus fludarabine, idarubicin, or topotecan at MD Anderson during the 1990s for AML in first relapse. These regimens are therapeutically equivalent.3 The daily doses of ara-C in these combinations are 1–2 g/m2 for 4 to 5 days. The MD Anderson patients were selected because they met the eligibility criteria for the gemtuzumab study: they had a first remission duration of at least 6 months, or at least 3 months if they were over age 60, had normal liver and kidney function, and had neither a preceding myelodysplastic syndrome nor secondary AML.1 The MD Anderson patients were not required to be CD33 positive while the gemtuzumab patients were so required. However, it is not clear that CD33 positivity is prognostic in this group of patients. The complete remission (CR) rates were 22% for gemtuzumab and 41% for the ara-C regimens. However, if one looks at a subgroup of patients who meet all criteria for CR except have platelet counts <100 000, but do not, however, require platelet transfusions (CRp), the frequency of such CRps was 16% in the gemtuzumab group and 0% in the ara-C regimen groups. It should be noted that although CRp may not convey the same survival advantage as CR, it does convey a survival advantage compared to patients who live a certain amount of time, eg 4–8 weeks, but achieve neither CR nor CRp.

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  1. University of Texas MD Anderson Cancer Center, Houston, TX, USA

    EH Estey

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This paper is part of a series of keynote addresses to be published in Leukemia. They were presented at the Acute Leukemia Forum, San Francisco, 20 April 2001. Supported by an unrestricted educational grant from Immunex.

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Estey, E. New drugs for therapy of AML. Leukemia 16, 306–309 (2002). https://doi.org/10.1038/sj.leu.2402375

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