Therapies are Rapidly Evolving for Patients With Newly Diagnosed AML

New York – At the 2018 Lymphoma & Myeloma congress, Gail Roboz, MD, Professor of Medicine, Director, Clinical and Translational Leukemia Programs, Weill Cornell Medicine, NewYork-Presbyterian Hospital, discussed therapies for patients with newly diagnosed acute myeloid leukemia (AML).

Until recently, treatment options for AML included cytarabine plus anthracycline, low-intensity chemotherapy, supportive care/hospice, or clinical trials. In the summer of 2017, a variety of drugs were approved in the treatment of AML, including midostaurin, CPX-351, enasidenib, gemtuzumab ozogamicin, and ivosidenib.

Dr Roboz explained that the cytarabine plus anthracycline therapy that had previously been the standard treatment has been beaten in 3 different randomized trials by the addition of gemtuzumab ozogamicin, the addition of midostaurin, and in comparison, to CPX-351.

Gemtuzumab ozogamicin was approved in 2001 for CD33-positive AML in patients with a first relapse who are aged 60 years or older and were not considered suitable candidate for other cytotoxic chemotherapy. In 2017 the drug was approved for adults with newly diagnosed CD33-positive AML as well as in patients older than 2 years with relapsed or refractory CD33-positive AML.

Midostaurin is approved for newly diagnosed AML that is FLT3 mutations positive as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation.

CPX-351 (daunorubicin and cytarabine liposome) is indicated for the treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes.

There are currently two FDA approved targeted therapies: enasidenib and ivosidenib. Dr Roboz emphasized the need to test patients for mutations before prescribing them targeted therapy, specifically with these two drugs.

“We want to get the testing done....It’s important to check your patients, especially those with relapsed disease,” she said.

Enasidenib is indicated for the treatment of adult patients with relapsed or refractory AML with an IDH2 mutation as detected by an FDA-approved test.

Ivosidenib is an IDH1 inhibitor indicated for the treatment of adult patients with relapsed or refractory AML with a susceptible IDH1 mutation as detected by an FDA-approved test.

Dr Roboz went on to discuss new targeted agents, not yet approved in AML including quizartinib and gilteritinib, which are second generation highly potent and selective FLT3 inhibitors.

“Highly potent and selective doesn’t necessarily mean better, but it means different, and importantly so,” said Dr Roboz.

She explained that quizartinib and gilteritinib demonstrated better results than salvage chemotherapy in phase 3 trials of relapsed and refractory AML.

Another novel targeted agent is glasdegib, an oral inhibitor of the Hedgehog signaling pathway, which improved overall survival in a randomized trial when combined with low-dose cytarabine versus low-dose cytarabine alone.

Lastly, she noted venetoclax, a selective inhibitor of BCL2, which is approved in CLL but not AML.  Venetoclax showed promising response rates in combination with azacitidine, decitabine, and low-dose cytarabine. These responses were seen across cytogenetic and molecular subgroups, including FLT3, IDH1/2, and TP53 mutations.

Dr Roboz is hopeful we will see FDA approvals for these drugs in the near future.

“All of these new drugs should make us enroll patients into clinical trials more, not less,” she concluded.—Janelle Bradley