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Under the Microscope: Making treatments more powerful—and more practical

For many people with cancer, receiving life-saving treatments such as chemotherapy requires hours of sitting in a clinic with an IV, day after day, over the course of many weeks. Wouldn’t it be better to simply take a pill at home?

New targeted therapies for patients with acute myeloid leukemia (AML) could allow some patients to do just that. The drugs, available in pill form, inhibit mutations in the IDH1 or IDH2 genes that are present in about 20% of AML patients. In addition to being more convenient, IDH inhibitors may be both more effective and have fewer side effects than conventional chemotherapy for patients with IDH mutations.

Courtney DiNardo, M.D., from MD Anderson Cancer Center, is one of the leading researchers developing IDH inhibitors and other AML treatments. With V Foundation funding, she set up a series of clinical studies aimed at making the best use of these promising therapies.

“We want to improve treatments by figuring out the best way to combine targeted IDH inhibitors with other treatments,” DiNardo explained. “Since the IDH inhibitors are in pill form, we are hopeful that the combined therapy will be more effective and also more convenient, and allow patients to remain in the comfort of their own homes during treatment.”

Overcoming resistance

DiNardo helped develop the first IDH1 and IDH2 inhibitors, which received FDA approval for use in leukemia patients with IDH mutations in the relapsed setting. However, researchers are still working to determine the optimal way to use these drugs. When used alone, the drugs tend to work well for a while, but then the cancer becomes resistant and begins to rebound.

“The best way to accomplish the most durable responses for patients and have their leukemia hopefully cured is by incorporating these single-agent targeted therapies with other effective cancer-directed therapies,” DiNardo said. “To figure out the best way to do this, we designed a group of clinical trials to test various combinations.”

Early results from some of these studies are very promising. In one study, researchers are administering a three-part regimen that includes the IDH1 inhibitor ivosidenib combined with two lower-intensity treatments that are the standard of care for older patients with AML.

“Responses from the first dozen or so patients to receive the ‘triplet’ regimen are phenomenal,” DiNardo said. “About 90% of these patients are showing cancer remission. This includes patients who are newly diagnosed as well as patients who have relapsed, where expectations for successful treatment are, unfortunately, lower.”

It’s too early to tell how long these responses will last, but the researchers are excited that early relapses are minimal and that the drug combination is well tolerated. This combination could eventually be administered at home since two of the three drugs are already available as a pill and the third drug has an oral formulation currently under evaluation. Additional clinical studies are examining a variety of other drug combinations, including a different triplet formulation in which all three drugs can be taken in pill form.

Giving patients options

One big benefit of having multiple clinical trials underway at one time is that doctors can select the best-fit trial for each patient. No matter where a person is in their cancer journey, they can likely find a trial that they’re eligible for and that best matches the unique characteristics of the patient and the leukemia. This is different from the traditional single-trial approach in which trials are designed for patients at a particular stage, such as all newly diagnosed patients or those who have relapsed.

The V Foundation support allowed me to develop a group of very meaningful clinical trials, rather than putting all of our resources into one specific trial. Running a program of clinical trials like this is not easy. It is expensive, challenging to organize and requires an enormous team. This funding helped me get this team together and put the whole process into place while laying the groundwork necessary to ensure ongoing and future support.

Courtney DiNardo, M.D.

The preliminary data and groundwork infrastructure made possible with the V Foundation project allowed DiNardo and her colleagues to secure additional funding support to continue and expand these clinical trials. They hope the studies will answer critical questions and allow more AML patients and families to benefit from the power and convenience of IDH inhibitors.