Eytan M. Stein, MD, director, Program for Drug Development in Leukemia, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, discusses the phase 1/2 KOMET-001 trial (NCT04067336) in relapsed/refractory acute myeloid leukemia (AML).

The phase 1/2 KOMET-001 trial is a first-in-human, dose-escalation study that is evaluating the tolerability of the menin inhibitor, KO-539 (ziftomenib) in patients with relapsed/refractory AML.

Although there is limited data currently available from the trial, findings shared at a previous meeting demonstrated KO-539 elicited responses, even in patients who did not have 

These initial findings prompted investigators to hypothesize whether menin inhibitors can be effective in patients with AML beyond the specific subgroup of patients with 

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Eytan M. Stein, MD, discusses the phase 1/2 KOMET-001 trial in relapsed/refractory acute myeloid leukemia.


Dr. Stein on the KOMET-001 Trial in Relapsed/Refractory AML

Eytan M. Stein, MD, director, Program for Drug Development in Leukemia, Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, discusses the key highlights of the phase 1/2 AUGMENT-101 trial (NCT04065399) in leukemias.

The phase 1 dose-escalation study is examining the maximum tolerated dose of SNDX-5613 in patients with leukemias harboring acute 

Preclinical data suggest that menin, an adapter protein, plays a role in the pathogenesis of 

-mutant leukemia, Stein says. Leukemia is driven by the upregulation of leukemogenic genes, and that occurs when menin binds to the KMT2A complex, Stein explains.

It is hypothesized that blocking the interaction between the menin and the MLL complex, those cells will not be primed to develop leukemia. Additionally, the leukemic cells transform into normal cells, Stein concludes.

Eytan M. Stein, MD, discusses the key highlights of the phase 1/2 AUGMENT-101 trial in leukemias.


Dr. Stein on Key Highlights of the AUGMENT-101 Trial in Leukemias

Eytan M. Stein, MD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses the importance of testing for measurable residual disease (MRD) in acute myeloid leukemia (AML). 

At the time of complete remission, the presence of MRD has been shown to be an adverse prognostic factor. Patients with MRD at the time of allogeneic bone marrow transplant have a higher risk of relapse following transplant than if they were MRD negative, says Stein. Notably, the presence of MRD also appears to predict risk of relapse for favorable-risk patients who are not undergoing transplant.

As such, clinical trials are needed to test agents that could induce MRD negativity, says Stein. Of equal concern will be the potential survival benefit and toxicities of the drug, concludes Stein. 

Eytan M. Stein, MD, discusses the importance of measuring for measurable residual disease in acute myeloid leukemia.

Dr. Stein on the Importance of MRD in AML

Eytan M. Stein, MD, internist, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses recent advances that have been made in the treatment of patients with acute myeloid leukemia (AML).

Over the past couple years, several new therapies have been approved for patients with AML. For patients with newly diagnosed disease, the combination of midostaurin (Rydapt) and chemotherapy serves as an option for those with 

-mutated disease. For patients who are unfit for induction chemotherapy, hypomethylating agents or low-dose cytarabine (LD-AraC) can be given in combination with venetoclax (Venclexta). Moreover, the hedgehog inhibitor glasdegib (Daurismo) can be used in combination with LD-AraC. CPX-351 is a liposomal formulation of daunorubicin and cytarabine and can be offered to patients with therapy-related AML and AML with myelodysplastic-related changes.

In the relapsed/refractory setting, physicians have access to 3 newly approved agents, including the IDH1 inhibitor ivosidenib (Tibsovo), the IDH2 inhibitor enasidenib (Idhifa), and the FLT3 inhibitor gilteritinib (Xospata). Physicians are also anticipating the FDA approval of quizartinib within the coming months for the treatment of patients with 

Dr. Stein on Recent Treatment Advances in AML

Eytan M. Stein, MD, internist, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses some of the potential combinations that could be explored with novel agents in the treatment of patients with acute myeloid leukemia (AML).

With several new agents in the pipeline for AML, Stein sees endless possibilities for combination regimens. One novel agent is midostaurin, which has demonstrated a 7% overall survival benefit at approximately 5 years when combined with induction chemotherapy for patients with 

Some clinical studies have examined combinations involving the BCL-2 inhibitor venetoclax (Venclexta), or the novel antibody-drug conjugate SGN-CD33A, paired with hypomethylating agents.

Overall, Stein sees this as a very exciting time in AML. There have not been any new drug approvals for this disease in the past several years, so many experts would agree that the field is now long overdue for one in the coming years.

Eytan M. Stein, MD, internist, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses some of the potential combinations that could be explored with novel agents in the treatment of patients with acute myeloid leukemia.

Eytan M. Stein, MD

Articles

Dr. Stein on the KOMET-001 Trial in Relapsed/Refractory AML

Dr. Stein on Key Highlights of the AUGMENT-101 Trial in Leukemias

Dr. Stein on the Importance of MRD in AML

Dr. Stein on Recent Treatment Advances in AML

Dr. Eytan Stein on Novel Combinations in AML