Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

Abstract

The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for "complete" remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial.

Keywords: AML; leukemia; neoplasm metastasis; relapse; salvage therapy.

Figure 1

Treatment algorithm for patients with RR-AML in 2015. There is no standard of care for the treatment of relapsed or refractory AML. A clinical trial is always the preferred option. The above algorithm is based on current clinical practice and will hopefully change in coming years due to improvements. In particular the targeted and immunotherapeutic agents detailed in this review may ultimately have utility in (1) initial therapy; (2) as a bridge to, or as a temporizing measure before, allo-HSCT; and/or (3) as part of consolidative therapy. * Achievement of a complete remission (CR) prior to undergoing alloHSCT is associated with best survival and is generally preferred. The survival of patients with residual disease undergoing alloHSCT varies considerably however and this therapy may be a reasonable option in selected patients not in CR [125]. HMA: Hypomethylating agent. LDAC: Low-dose cytosine arabinoside. Allo-HSCT: Allogeneic Hematopoietic Stem Cell Transplant.