Alice S. Mims, MD, medical oncologist, Department of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center—James, discusses the Beat AML Master Trial in acute myeloid leukemia (AML).

A lot of the newer targeted therapies are exciting, but not curative, says Mims. The field needs to do a better job of curing patients rather than extending their survival, Mims adds.

To that end, the Beat AML Master Trial, led by the Leukemia and Lymphoma Society, is looking at an older population of patients with AML, mostly those who are 60 years and older. These patients will undergo molecular testing, and results are received within 1 week. Patients who have dominant clones are put on particular therapies. If the patient doesn’t have targetable mutations, they are given investigational therapy. That trial has shown some exciting results and, hopefully, will lead to new therapies in that patient population, concludes Mims.

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Alice S. Mims, MD, discusses the Beat AML Master Trial in acute myeloid leukemia (AML).

Dr. Mims on the Beat AML Master Trial in AML

Alice S. Mims, MD, medical oncologist, Department of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center—James, discusses her recommendations regarding holding therapy until molecular test results are received for symptomatic patients with acute myeloid leukemia (AML).

Whether a symptomatic patient waits for their molecular testing results depends on their molecular profile, explains Mims. Patients with proliferative disease who have high white blood counts, require leukapheresis, or have symptoms of disseminated intravascular coagulation may want to start treatment because it is not safe to wait, says Mims.

For most patients, it takes at least 1 week to receive molecular profiling results. Midostaurin (Rydapt), which is approved for patients with newly diagnosed, FLT3-mutatied AML, is not started until day 8 after 7+3 therapy starts. Therefore, it is appropriate to wait to start targeted therapy. For other targeted therapeutics, when a patient should start therapy depends on the setting, concludes Mims.

Alice S. Mims, MD, discusses her recommendations regarding holding therapy until molecular test results are received for symptomatic patients with acute myeloid leukemia.

Dr. Mims on Waiting for Molecular Tests Before Starting Therapy in AML

Alice S. Mims, MD, medical oncologist, Department of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center—James, discusses the emergence of targeted therapy in acute myeloid leukemia (AML) treatment.

The introduction of targeted therapies, including IDH inhibitors and FLT3 inhibitors, has greatly changed the AML treatment paradigm, particularly the approval of enasidenib (Idhifa), ivosidenib (Tibsovo), and gilteritinib (Xospata), among others, explains Mims.

FDA approved the IDH2 inhibitor enasidenib

 for the treatment of patients with IDH2-mutated relapsed/refractory AML. A little over 2 years later, the IDH1 inhibitor 

 in May 2019 for newly diagnosed patients who are ineligible for intensive chemotherapy who are ages 75 or older; it is also approved in the relapsed/refractory setting. The FLT3 inhibitor 

 in November 2018 to treat patients who have FLT3-ITD— or FLT3-TKD–mutated relapsed/refractory AML.

Alice S. Mims, MD, discusses the emergence of targeted therapy in acute myeloid leukemia treatment.

Dr. Mims on the Emergence of Targeted Therapy in AML

Alice S. Mims, MD, medical oncologist, Department of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center—James, discusses developed resistance in acute myeloid leukemia (AML).

With a lot still unknown about resistance in AML, the most is known about patients with 

 and FLT3 mutations, explains Mims. Patients with 

-mutated AML often have other mutations, such as 

 mutations. This patient population may not respond well to 

 inhibitors alone, which is being explored through research regarding whether there are better combination therapies that can be used upfront, says Mims.

Some patients develop resistance mutations after being treated with 

 inhibitors. For example, a patient may start with an 

 mutation. When patients stop responding to treatment that has previously been effective, it is important to repeat molecular profiling to see if patients have acquired new mutations, concludes Mims.

Alice S. Mims, MD, discusses developed resistance in acute myeloid leukemia.

Dr. Mims on Developed Mutations in AML

Alice S. Mims, MD, medical oncologist, Department of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center—James, discusses up front molecular profiling in patients with newly diagnosed acute myeloid leukemia (AML).

Up front molecular testing is recommended by the National Comprehensive Cancer Network, explains Mims. The discussion surrounding this topic is largely whether or not to wait for the test results before initiating treatment.

Some patients who have rapid disease progression are unable to wait for results, says Mims. However, other patients who have a relatively low disease burden may benefit from waiting for the results before starting treatment. The results may indicate the patient is a candidate for targeted therapy rather than chemotherapy, concludes Mims.

Alice S. Mims, MD, discusses up front molecular profiling in patients with newly diagnosed acute myeloid leukemia.

Dr. Mims on Performing Molecular Profiling at Diagnosis in AML

Alice S. Mims, MD, assistant professor of medicine, The Ohio State University Comprehensive Cancer Center, discusses momelotinib in patients with myelofibrosis.

The SIMPLIFY-1 study investigated momelotinib to determine if it was non-inferior to ruxolitinib (Jakafi). It did show non-inferiority of splenic size for patients with myelofibrosis, states Mims.

The SIMPLIFY-2 attempted to determine if momelotinib was superior to ruxilitinib. It was not superior but there was improvement in anemia. There will be some role for momelotinib in the future for these patients, states Mims.

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Dr. Mims Discusses Momelotinib in Myelofibrosis

Alice S. Mims, MD, assistant professor of medicine, Ohio State University Comprehensive Cancer Center, discusses the current challenges with myelofibrosis.

Most patients are not candidates for allogeneic transplants, which is the only myelofibrosis therapy. In addition, there is no therapy that has proven to reverse fibrosis.

Only about 10% to 20% of patients with myelofibrosis show signs of myelofibrosis risk factors prior to diagnosis. The risk factor is if you have another myeloid malignancy, specifically myeloproliferative disorders, such as polycythemia vera or essential thrombocythemia.

Alice S. Mims, MD