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Future ‘very bright’ in acute myeloid leukemia
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NEW YORK — Treatment options for acute myeloid leukemia have evolved rapidly, but the expanded armamentarium has created a new set of challenges, according to a presenter at HemOnc Today New York.
“The field of AML is moving very quickly. Decision-making has gotten less straightforward because we have more options, but that is a good thing rather than a bad thing,” Alexander E. Perl, MD, associate professor in the leukemia program at Abramson Cancer Center at University of Pennsylvania, said during a presentation.
The mainstay of AML treatment for several decades had been the “7 + 3” induction chemotherapy regimen. This treatment consists of 7 days of cytarabine, followed by 3 days of either daunorubicin or idarubicin.
However, the FDA has granted nine approvals for AML in the past 2 years.
“We used to think in terms of getting patients started on therapy as quickly as possible because there was only one treatment regimen,” Perl said. “Now that we have new options, we have to think about how we can get the right tests that will drive the right treatment choice.”
Five of the recent FDA approvals applied to agents indicated for frontline therapy. These include midostaurin (Rydapt, Novartis) plus daunorubicin/cytarabine; gemtuzumab ozogamicin (Mylotarg, Pfizer) with or without intensive chemotherapy; daunorubicin and cytarabine liposome for injection (Vyxeos, Jazz Pharmaceuticals), also called CPX-351; venetoclax (Venclexta; AbbVie, Genentech) plus hypomethylating agents or low-dose cytarabine; and glasdegib (Daurismo, Pfizer) plus low-dose cytarabine.
“We’re now using genetics quickly to guide therapy rather than to just risk-stratify patients,” Perl said. “That’s important, because our patients are benefitting in ways they never did before.”
One example of this is midostaurin, approved for FLT3-mutant AML.
FLT3 mutations are present in approximately one-third of patients with AML.
FLT3/ITD mutations are associated with high risk for relapse. Allogeneic transplant seems to lower the risk for relapse considerably, so many of these patients go on to transplant once they achieve remission.
“It is important to integrate FLT3 mutation testing in frontline diagnostics and quickly act on the results,” Perl said.
Another significant advance has been the incorporation of venetoclax — a BCL2 inhibitor — into treatment for older adults, Perl said.
“It is exciting that we can use not just the traditional cytotoxic agents, but agents that are mutation-targeted and drugs that target biologic processes,” Perl said. “This means more patients are able to be treated. From the community perspective, this will change who you can see and what you can offer. It used to be, for older patients, we’d largely only be able to offer supportive care as kind of a Band-Aid for their disease, but now we can offer therapy that can induce remission, pretty much without regard to age.”
New approvals for the relapsed/refractory setting include ivosidenib (Tibsovo, Agios), an IDH1 inhibitor; enasidenib (Idhifa; Celgene, Agios), an IDH2 inhibitor; and gilteritinib (Xospata, Astellas), an FLT3 inhibitor.
The treatment advances in the past couple years mean more patients can be offered therapy, they are surviving longer, and many are experiencing less toxicity, Perl said.
The best therapies are yet to come, he added.
“We’re on the right track, and the future is very bright in AML,” he said. “One of the reasons for excitement with all of these drugs is, what will combination studies look like? Also, hopefully we’ll soon start to see immunotherapy successes like we have in many solid tumors.” – by Mark Leiser
Reference:
Perl A. AML: Progress — finally? Presented at: HemOnc Today New York; March 21-23, 2019; New York.
Disclosure: Perl reports consultant fees, honoraria for advisory board service, or research funding to his institution from AbbVie, Actinium Pharmaceuticals, Agios, Arog, Astellas, Bayer, BioMed Valley Discoveries, Daiichi Sankyo, FujiFilm, Jazz Pharmaceuticals, Novartis, NewLink Genetics and Takeda.