Several novel therapies are being developed as treatments for patients with acute myeloid leukemia (AML), based on disease biology, explains Raoul Tibes, MD. The agent AG-221, that targets IDH2, is currently under development and has shown promising responses for patients with AML. IDH1 and IDH2 mutations are found in 10% to 20% of patients with AML, Tibes notes. In addition to IDH inhibitors, several other novel treatments are currently in development for patients with AML, such as DOT1L inhibitors, CD33 monoclonal antibodies, and other therapeutics.

Newer treatments are also showing promise for patients with FLT3-positive disease, says Tibes. Of all the novel agents, FLT3 inhibitors are furthest along in their clinical development in AML, notes Jeffrey Lancet, MD. Studies are assessing the FLT3 inhibitor quizartinib as a single-agent and in combination with hypomethylating agents, such as azacitidine. In a phase I study of this combination, in patients with FLT3-ITD-positive relapsed/refractory AML or myelodysplastic syndromes (MDS), the overall response rate was 82%.

The multikinase inhibitor sorafenib has also been found to block FLT3 in AML. In a phase II study of 267 patients with newly diagnosed AML, the combination of sorafenib and chemotherapy demonstrated efficacy in newly diagnosed patients with AML, regardless of FLT3 mutation status. The median event-free survival (EFS) was 20.5 months with sorafenib compared with 9.2 months for patients receiving placebo (P = .013).

In addition to targeted therapies, a number of next-generation cytotoxic agents are under development, notes Lancet. Although traditional chemotherapy has not offered curative potential, two potential new chemotherapeutic agents have demonstrated promise. Vosaroxin in combination with cytarabine demonstrated intriguing findings in the phase III VALOR trial for patients with first relapsed or refractory AML, Lancet notes. The median overall survival (OS) was 7.5 months with vosaroxin compared with 6.1 months with placebo; however, this difference was not statistical significance (P = .06).

The second cytotoxic of interest, CPX-351, recently was granted a fast track designation as a treatment for elderly patients with relapsed AML. CPX351 is a liposomal encapsulation whose fixed molar ratio of cytarabine and daunorubicin is felt to optimize drug delivery, explains Lancet. In phase II studies, the complete response rate with CPX-351 was 66.7% versus 51.2% with standard chemotherapy (P = .07). Median EFS and OS were also higher in the CPX-351 arm at 6.5 versus 2.0 months and 14.7 versus 12.9 months, respectively.

Immunotherapy is beginning to emerge as a potential treatment option for patients with AML, specifically modified T cell therapy, notes Mark R. Litzow, MD. The two most promising therapies at this time are chimeric antigen receptor (CAR)-modified T cell therapies and bispecific NK cell engagers (BiKEs).