New drugs for AML
Azacytidine and decitabine are lipid-lowering drugs that inhibit protein and DNA synthesis, respectively; clinical trials with these drugs have evidenced prolonged survival of between 5 months and 2 years in patients over 65.
Sorafenib, midostaurin, and quizartinib are 3 drugs that inhibit the development of the FLT3 mutation (the mutation that leads to malignancy and poor prognosis in AML). They have been used in clinical trials (given together with azacytidine) to assess tolerance and treatment response in patients with the disease.
Volasertib was used in phase-I clinical trials in patients with refractory AML, and a response was observed. For this reason, it is currently being used in phase-III trails in combination with LDARAC to see if there is an improvement in response.
The search for monoclonal antibodies that are useful in this disease is ongoing, and efforts are being made to reconsider gemtuzumab ozogamicin and its effectiveness given the antibody's ability to target most AML cells. However, because initial studies have shown that it is not widely effective, leading it to be ruled out. New studies have found gemtuzumab to have certain usefulness.
Use of immune checkpoint inhibitors is also being studied for treatment of AML. These drugs block systems the defense systems of tumor cells against the patient's immune system, thus allowing the patient's defenses to eliminate the tumor cells.
Applying chimeric antigen receptors (CARs) to AML is proving to be a challenge. CARs are patient immune cells that have been manipulated to target a relatively specific target in tumor cells. They are very effective in acute lymphoid leukemia and chronic lymphocytic leukemia. There is still no good target allowing for the disease to be eliminated without causing sever toxicity.
Another option for manipulating the immune system is to use vaccines that target AML. Some preliminary data have become available on targeting the Wilms tumor protein.
Many other drugs are being developed which may be applied to specific subtypes of AML that exhibit concrete molecular alterations, such as IDH inhibitors in patients carrying the mutation. This type of treatment is based on specific alterations present in each patient. The treatment is begun once certain changes are detected when there is a drug available to neutralize the pernicious effect.