The mortality rate associated with acute myeloid leukemia (AML) is approximately 80%, with even higher rates found among certain patient groups including older adults.1 AML mortality rates are reportedly increasing because of the growing population of adults living into advanced age, underscoring the need for effective treatment approaches.1 After decades of stagnation, the introduction of several new therapies in the past few years have presented new opportunities to improve AML treatment.1-3
In a review published in Blood, Susan E. DeWolf, MD, from Memorial Sloan-Kettering Cancer Center in New York, New York, and Martin S. Tallman, MD, of Weill Cornell Medical College in New York, New York, discussed the evolving landscape of treatment for patients with relapsed or refractory AML, a population with 5-year overall survival rates of 10%. They noted the lack of a uniform treatment strategy for this group, with the exception of allogeneic hematopoietic cell transplantation (HCT) as the only potentially curative treatment option for patients achieving a second complete remission.3
The authors described the strategies they currently employ in the treatment of relapsed or refractory AML outside of clinical trials, stating that their approach “increasingly relies on specific disease biology…. Primarily [considering] age, fitness to tolerate intensive chemotherapy, remission duration, and presence of a targetable mutation to guide treatment.”
In their paper, Dr DeWolf and Dr Tallman used several case studies to illustrate various treatment considerations such as the selected points highlighted below.
Early Relapsed AML in a 30-Year-Old Patient
While there is a general shift away from traditional cytotoxic chemotherapy in AML treatment, De Wolf and Tallman explained that they utilize this approach in the case of “early relapse in a young patient whose leukemia cells do not express a targetable mutation in whom cure with allogeneic HCT is the clear goal.”3 They now use high-dose cytarabine (HiDAC) less frequently in order to minimize the risk of associated toxicities and other adverse effects. Two alternate regimens they often consider are mitoxantrone/etoposide/cytarabine (MEC) and fludarabine/cytarabine/granulocyte colony-stimulating factor/idarubicin (FLAG-IDA).
For young patients in first relapse who have a FLT3-ITD mutation, the authors favored the use of the FLT3 inhibitor, gilteritinib, depending on the patient’s disease course and biology. This consideration is based on results from the ADMIRAL trial of gilteritinib in patients with primary refractory or first relapse FLT3-mutated disease in which the median overall survival was 9.3 months with gilteritinib monotherapy vs 5.6 months with reinduction chemotherapy (low-dose cytarabine, azacitidine, 180 MEC, or FLAG-IDA).3,4
In November 2018, the US Food and Drug Administration approved gilteritinib for the treatment of relapsed or refractory FLT3-mutated AML; however, the “poor survival rate in either group in the ADMIRAL study is conspicuous,” despite the initial promise of these treatment regimens. Other research has demonstrated a benefit for FLT3 inhibition as maintenance therapy after allogeneic HCT, and a trial is currently in progress to explore this further.