Acute myeloid leukemia (AML) is the most common form of acute leukemia, with an incidence that increases with advanced age. AML is a remarkably complex malignancy, with considerable genetic, epigenetic, and phenotypic heterogeneity. Patients can be stratified into favorable-, intermediate-, and adverse-risk groups based on their cytogenetic profile. Although the introduction of targeted therapies administered in combination with chemotherapy has improved the rate of complete remission (CR), rates of relapse have not changed and remain the most important cause of treatment failure in the postconsolidation or post-transplantation setting. The most effective postremission therapy continues to be allogeneic hematopoietic cell transplantation (alloHSCT). There is an emerging need to identify other effective and safe postremission therapeutic approaches.
In a critical review published in the American Journal of Hematology, Tapan Mahendra Kadia, MD, of the department of leukemia at the University of Texas MD Anderson Cancer Center in Houston, and colleagues summarized current literature surrounding maintenance treatment in patients with AML in the postconsolidation and post-transplantation settings.
Maintenance Therapy Following Consolidation
Typically, patients who continue therapy after achieving CR post-consolidation do so with the goals of prolonging response and improving overall survival (OS), especially those patients who are ineligible for alloHSCT. However, toxicity remains an issue and can lead to premature drug discontinuation.
Several studies have investigated the role of low-dose cytarabine-based chemotherapy maintenance, most of which were conducted during the 1980s. Results from these studies, however, are difficult to interoperate; not only did the study populations have different clinical and biological baseline characteristics compared with patient populations used in modern studies , but different induction and consolidation treatments were also administered. Nevertheless, disease-free survival (DFS), but not OS, was found to improve.
Hypomethylating agents were assessed in 2 large scale studies: the UK NCRI AML16 and HOVON97 trials. In these studies, DFS advantage was demonstrated but no OS benefit was found. However, the UK NCRI AML16 study did show that patients with negative measurable residual disease (MRD) at the end of consolidation had better outcomes after azacitidine maintenance therapy.
Immunotherapy may also be an option. Several studies such as the UKMRC AML11 trial and a multicenter Finnish study have described the antileukemic activity of interferon that arises from direct apoptosis of leukemic blasts and immune activation. However, no benefit has been seen with respect to relapse, DFS, or OS. Interleukin-2, which increases the cytotoxic effect of natural killer (NK) cells, was also investigated in a large Swedish trial involving adults with AML who had achieved CR at least once. No OS benefit was demonstrated, but 3-year DFS was found to be significantly improved in the maintenance group (40% vs 26%; P <.01). Based on these data, in 2008, interleukin-2 was approved for remission maintenance in adults with AML in CR1 by the European Medicines Agency.
Lenalidomide has been widely employed in clinical trials due to its immunomodulation-based antileukemic effect. However, it was found to be ineffective in improving outcomes, even when combined with azacitidine. Gemtuzumab ozogamicin, a humanized anti-CD33 monoclonal antibody conjugated with calicheamicin, was found to be ineffective as well. However, the MDACC group has reported promising preliminary data about the use of nivolumab in patients with high-risk who are in CR and are ineligible for alloHSCT, with 12- and 18-month estimated OS of 86% and 67%, respectively.