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Emerging Treatment Options Improve Odds for Older Patients With AML

Caroline Seymour
Published: Thursday, Mar 07, 2019

Richard M. Stone, MD

Richard M. Stone, MD

A plethora of additional agents has given physicians more options for the treatment of older patients with acute myeloid leukemia (AML), explained Richard M. Stone, MD, although the optimal combinations and settings have yet to be discerned.

In terms of combinations, venetoclax (Venclexta) and hypomethylating agents (HMAs) have shown strong signals of activity. In a phase II trial reported at the 2018 ASH Annual Meeting, the combination of venetoclax and 10 days of decitabine induced a complete response (CR) rate or a CR with incomplete hematologic recovery of 92% in patients >60 years with newly diagnosed AML and 71% of patients with secondary AML.

“The therapeutic algorithm has changed from 7 + 3 chemotherapy for fit patients and azacitidine or decitabine for unfit patients to a more personalized approach,” said Stone, director of the Adult Leukemia Program at Dana-Farber Cancer Institute.

Additional agents include midostaurin (Rydapt) for patients with FLT3-mutant AML, gemtuzumab ozogamicin (Mylotarg) for patients with t(8;21) or inv(16), and CPX-351 (Vyxeos) for patients with therapy-related AML or AML from myelodysplastic syndrome (MDS), with a carrier type similar to MDS, or with MDS-related dysplastic changes.

This departure from a chemotherapy approach is due in large part to refined patient assessments and a better understanding of the biology of AML.

“We can’t stop now. We have to keep working to find out how to use them, make them less toxic, and more effective,” Stone said. “Our older adults need that.”

In an interview with OncLive, Stone, who is also a professor of medicine at Harvard Medical School, discussed the therapeutic landscape for elderly patients with AML.

OncLive: How has the management of elderly patients with AML evolved in recent years?

Stone: Thanks to the amazing number of newly FDA-approved drugs in AML, we have new options for older patients with the disease. We’ve seen the impact of genetics on prognosis and maybe even choice of therapy in certain cases.

Before we get to the new drugs, I want to make sure that people realize that there are different ways to assess the patient and the disease right now. In terms of patient assessment, we have to be good communicators and make sure we transmit what we know to the patient and their family. These are very stressed patients who can’t really hear what we say, so we have to avoid medical jargon when possible. Patients inflate what we tell them because the devastating news about their leukemia is hard to put into one’s own psyche.

Could you elaborate on patient assessment?

Patient assessment includes more than just performance status or whether we think they’re fit or unfit. A lot of research led by the late Arti Hurria, MD, of City of Hope, used something called the geriatric assessment scale. That may be better than [another test] that looks at the patient’s ECOG performance status or Karnofsky scales to assess their fitness for chemotherapy. Preliminary work has shown that the geriatric assessment, which is a battery of questions about social functioning, ability to do tasks, and physical tests, can predict a patient’s likelihood of success or failure with chemotherapy.

On the other hand, we [also have] these new tests that stress the [importance of] genetics. From work done by R. Coleman Lindsley, MD, PhD, of Dana-Farber Cancer Institute, we know that mutations can guide the prognosis and perhaps help us choose therapy. You can bucket these patients into 3 categories. When I say “these patients,” I mean older adults who don’t appear to have a history of myelodysplasia or other cancers before their AML.

One bucket would be those with p53 mutations. Another bucket would be those with MDS-type mutations or secondary mutations––epigenetic mutations such as ASXL1. The third bucket would be those who have what we tend to call pan-AML mutations or more secondary, singling-type mutations in the RAS or FLT3 pathway. The latter group are the ones with de novo mutations in the singling pathway who do pretty well with 7 + 3 chemotherapy. Patients with p53 and secondary mutations don’t do very well.

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