Novel Mechanisms for Post-Transplant Maintenance Therapy in Acute Myeloid Leukemia

Abstract

Allogeneic stem cell transplantation has improved survival for patients with acute myeloid leukemia (AML), especially for patients with disease at high risk of relapse. However, relapse remains the most common cause of treatment failure and death in the post-transplant period. Maintenance therapy, an extended course of treatment after achieving remission to reduce the rate of relapse, is an important component of the treatment of various hematologic malignancies; however, its role in the treatment of AML is far less well-defined. Recently, there has been significant interest in the use of novel therapeutic agents as maintenance therapy after allogeneic stem cell transplant, utilizing new mechanisms of treatment and more favorable toxicity profiles. In this review, we will discuss the mechanistic and clinical data for post-transplant maintenance therapies in AML. Then, we will review several emergent and current clinical trials which aim to incorporate novel agents into maintenance therapy regimens.

Literature review and expert opinion on the treatment of high-risk acute myeloid leukemia in patients who are eligible for intensive chemotherapy

“…Such strategy may be advantageous in those patients with high-risk of post-transplant relapse, including those with an MRD positive status. Multiple studies have been conducted regarding the use of a myriad of agents in the post-alloSCT maintenance setting, in some cases with promising results ( 96 ). In a retrospective study from Ali et al., post-alloSCT azacitine maintenance therapy improved EFS and OS in patients receiving reduced-intensity transplant ( 97 ).…”

Post-Transplant Maintenance Therapy in Acute Myeloid Leukemia

“…Acute myeloid leukemia (AML) is a heterogeneous group of blood cell cancers that arise from the clonal expansion of malignant hematopoietic precursor cells in the bone marrow, which contributes to the aggressive nature of this cancer [ 1 ]. The prognosis varies based on age, comorbidities, and cytogenic and mutation status [ 1 , 2 , 3 ]. Treatment is initiated with standard induction chemotherapy to induce a complete remission (CR) which will be followed by consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HCT) depending on disease risk based on cytogenetic and molecular aberrations at presentation and response to therapy assessed by measurable residual disease (MRD) at the time of transplant, donor availability, comorbidities, age, and performance status [ 1 , 2 , 3 ].…”

“…The prognosis varies based on age, comorbidities, and cytogenic and mutation status [ 1 , 2 , 3 ]. Treatment is initiated with standard induction chemotherapy to induce a complete remission (CR) which will be followed by consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HCT) depending on disease risk based on cytogenetic and molecular aberrations at presentation and response to therapy assessed by measurable residual disease (MRD) at the time of transplant, donor availability, comorbidities, age, and performance status [ 1 , 2 , 3 ]. If the patient is determined to have intermediate- or adverse-risk AML, allo-HCT is strongly recommended.…”

“…Unfortunately, the risk of relapse has not seen the same degree of reduction over the past several years. Now, the focus of recent research has shifted to investigating different approaches to prevent relapse after allo-HCT since around 20–30% of patients with AML will relapse in the first 1–2 years following allo-HCT and a shorter time to relapse is correlated with worse outcomes [ 1 , 2 , 3 , 6 ]. After relapse, the prognosis is poor, and the median survival is only 4–6 months, with a 1-year survival rate of less than 20% [ 1 , 2 , 3 , 6 ].…”

“…Now, the focus of recent research has shifted to investigating different approaches to prevent relapse after allo-HCT since around 20–30% of patients with AML will relapse in the first 1–2 years following allo-HCT and a shorter time to relapse is correlated with worse outcomes [ 1 , 2 , 3 , 6 ]. After relapse, the prognosis is poor, and the median survival is only 4–6 months, with a 1-year survival rate of less than 20% [ 1 , 2 , 3 , 6 ]. These figures represent the importance of identifying strategies to decrease rates of relapse and improve post-transplant survival.…”