Promising New Regimens for Treating Acute Myeloid Leukemia

Alice S. Mims, MD, MSCR, a hematologist at The Ohio State University Comprehensive Cancer Center, discusses new regimens for treating patients with acute myeloid leukemia (AML), including anti-CD47 immunotherapy, IDH inhibitors, and menin inhibitors.

Mims says that immunotherapies targeting CD47 show promise in AML, with the anti-CD47 antigen magrolimab combined with azacitidine (Onureg) showing high responses in patients with both wild-type AML and TP53-mutated AML in the phase 1b ENHANCE-2 trial (NCT03248479). TP53-mutated disease has unmet treatment needs because it does not respond to standard-of-care regimens.

Another significant area of interest to Mims is IDH inhibitors, which are being investigated in the randomized placebo-controlled phase 3 HOVON150AML trial (NCT03839771) from the Hemato Oncology Foundation for Adults in the Netherlands (HOVON) and the German-Austrian AML Study Group (AMLSG). This trial is exploring the efficacy of ivosidenib (Tibsovo) or enasidenib (Idhifa) in addition to intensive induction chemotherapy, followed by consolidation therapy and maintenance therapy with IDH inhibitor (NCT03839771).

Finally, Mims says that menin inhibitors are an important area of research, especially for NPM1-mutated AML and mixed-lineage leukemia (MLL)-rearranged AML. The ongoing phase 1/2a KOMET-001 trial (NCT04067336) is investigating the KMT2A (MLL) inhibitor KO-539. According to Mims, menin inhibitors are being investigated in the upfront setting in combination with hypomethylating agents, BCL-2 inhibitors, and intensive induction chemotherapy.

TRANSCRIPTION:

0:08 | I think some of the regimens that we're excited about, one in particular, is targeting CD47, like magrolimab. That seems to have potentially increased responses in TP53-mutated AML. And I think that population doesn't respond well to any of our typical treatment regimens. So, that's really the patient population we want to do a better job with. So as we're seeing potential therapies that may help that population, we're all very excited about that.

0:44 | I think some other regimens that will be exciting [are] having the IDH inhibitors combined with intensive induction therapy in the upfront setting. HOVON’s doing the randomized phase 3 placebo-controlled trial, looking at if that will make a difference.

I think a lot of us are excited about menin inhibitors, in particular for NPM1-mutated AML and MLL-rearranged AML as that those agents have shown single-agent activity in the relapsed/refractory setting. And so, as more data evolves with those inhibitors, I think people are excited to see how they'll do in the upfront setting combined with either hypomethylating agents and BCL-2 inhibitors or with intensive induction therapy as well.