Recent Treatment Advances and the Role of Nanotechnology, Combination Products, and Immunotherapy in Changing the Therapeutic Landscape of Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is the most common acute leukemia that is becoming more prevalent particularly in the older (65 years of age or older) population. For decades, “7 + 3” remission induction therapy with cytarabine and an anthracycline, followed by consolidation therapy, has been the standard of care treatment for AML. This stagnancy in AML treatment has resulted in less than ideal treatment outcomes for AML patients, especially for elderly patients and those with unfavourable profiles. Over the past two years, six new therapeutic agents have received regulatory approval, suggesting that a number of obstacles to treating AML have been addressed and the treatment landscape for AML is finally changing. This review outlines the challenges and obstacles in treating AML and highlights the advances in AML treatment made in recent years, including Vyxeos®, midostaurin, gemtuzumab ozogamicin, and venetoclax, with particular emphasis on combination treatment strategies. We also discuss the potential utility of new combination products such as one that we call “EnFlaM”, which comprises an encapsulated nanoformulation of flavopiridol and mitoxantrone. Finally, we provide a review on the immunotherapeutic landscape of AML, discussing yet another angle through which novel treatments can be designed to further improve treatment outcomes for AML patients.

New directions for emerging therapies in acute myeloid leukemia: the next chapter

“…The current treatment paradigm employs remission-inducing chemotherapy, with cytarabine and anthracycline with or without a purine analogue, such as 7 days of standard-dose cytarabine plus 3 days of anthracycline (ie, “7 + 3”), fludarabine–Ara-C–granulocyte colony-stimulating factor–idarubicin, or similar induction, followed by consolidation chemotherapy and/or allogeneic stem cell transplantation (SCT) for patients with a high risk of relapse 5 . This approach has been the mainstay of therapy for the past four decades, achieving complete remission (CR) in 60–80% of patients <60 years of age.…”

“…This approach has been the mainstay of therapy for the past four decades, achieving complete remission (CR) in 60–80% of patients <60 years of age. Although effective, this approach may be poorly tolerated, with a higher risk of induction mortality in patients with comorbidities, poor performance status, and/or advanced age 5 – 7 . In addition, unsatisfactory response rates and survival have been reported for conventional chemotherapy in patients with adverse cytogenetic risk or high-risk molecular mutations, such as TP53 (refs.…”

Bcl‐2‐associated athanogene 5 overexpression attenuates catecholamine‐induced vascular endothelial cell apoptosis

“…Recently, increasing studies have demonstrated that inhibition of ER stress had great benefits on the ischemic injured cardiomyocytes (K. T. J. Chen, Gilabert-Oriol, Bally, & Leung, 2019;Shi et al, 2016). Therefore, targeting ER stress might be a promising strategy for treating cardiovascular disorder including hypertension (Walraven et al, 2018).…”

The regulation of nanomaterials and nanomedicines for clinical application: current and future perspectives

“…In particular Vyxeos® has proven very successful in the treatment of adult acute myeloid leukemia. 65 Vyxeos® is a liposomal formulation of daunorubicin and cytarabine. In the phase 3 trials, Vyxeos® demonstrated superior overall survival and reduced risk of death in patients compared to those who were administered the two drugs in a combination regime with no nanotechnology.…”