Integrating Menin Inhibitors Into AML Care: Patient Selection, Toxicity Management, and Future Directions

In this interview with Pharmacy Times at Oncology Pharmacists Connect in Austin, TX, Bernard Marini, PharmD, BCOP, FHOPA, Inpatient Hematology Clinical Pharmacist, University of Michigan, discusses the growing role of menin inhibitors in the treatment of acute myeloid leukemia (AML). He highlights key molecular alterations associated with response to these agents, including KMT2A rearrangements, NPM1 mutations, and NUP98 rearrangements, and reviews how menin inhibitors may expand from relapsed or refractory settings into frontline treatment strategies. Marini also outlines important monitoring considerations, emphasizing differentiation syndrome, QT prolongation, myelosuppression, and liver function abnormalities as key toxicities requiring pharmacist oversight.

Pharmacy Times: As menin inhibitors enter clinical practice, what molecular and clinical factors are most important when identifying patients who may be appropriate candidates for these therapies, and how do you envision them fitting into current AML treatment pathways?

Bernard Marini, PharmD, BCOP, FHOPA: For menin inhibitors, the most important abnormalities that identify patients who may benefit from these therapies are KMT2A rearrangements, NPM1 mutations, and NUP98 rearrangements. These are the patient populations that are most likely to benefit from menin inhibitor therapy.

Currently, menin inhibitors have demonstrated strong efficacy in the relapsed and refractory setting among patients with these molecular alterations. However, emerging data are increasingly supporting the use of menin inhibitors in combination with either low-intensity therapy or intensive chemotherapy in the frontline setting.

At present, these agents are primarily used as single agents or, in some cases, in combination with low-intensity therapies. As additional data become available, menin inhibitors may move into the frontline treatment setting for patients with these mutations and cytogenetic abnormalities.

Pharmacy Times: Menin inhibitors introduce unique monitoring and supportive care considerations. What toxicities should oncology pharmacists be particularly aware of, and what strategies can help proactively manage these adverse events to keep patients on therapy?

Marini: I think the most important toxicity clinicians need to be aware of with menin inhibitors is differentiation syndrome. Fortunately, pharmacists have been managing differentiation syndrome with a variety of oncology agents for many years, particularly with therapies such as arsenic trioxide and all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), as well as with IDH inhibitors. As a result, pharmacists are generally well equipped to recognize and manage differentiation syndrome. It is simply important to understand that this toxicity can also occur with menin inhibitors.

We also see QT interval prolongation with these agents. This adverse effect appears to be more common with certain menin inhibitors than others, and we will likely gain a better understanding of those differences as more comparative data become available.

In addition to differentiation syndrome and QT interval prolongation, other clinically relevant toxicities include myelosuppression and mild liver function test abnormalities. These are the key adverse effects that clinicians are likely to encounter in practice when using menin inhibitors.

Pharmacy Times: Because menin inhibitors are oral therapies, access, adherence, and care coordination can present significant challenges. What workflow strategies have you found most effective for ensuring timely treatment initiation and continuity of care across inpatient and outpatient settings?

Marini: For timely treatment initiation, one of the most important workflows has been identifying these molecular abnormalities as early as possible. At our center, we expedite cytogenetic and molecular testing so that we can quickly determine which patients may be eligible for menin inhibitor therapy, particularly in the context of clinical trials.

It is also critical to ensure timely access to these agents. To accomplish this, we involve our oral chemotherapy teams, pharmacy technicians, and the broader multidisciplinary care team early in the process. Their involvement helps ensure that patients have appropriate insurance coverage and that any financial or access-related barriers are addressed as quickly as possible.

Establishing these workflows has been essential for facilitating timely treatment initiation and improving access to therapy for eligible patients.

Pharmacy Times: Given your role in inpatient hematology, how do you see oncology pharmacists contributing to multidisciplinary decision-making when integrating menin inhibitors into AML care, particularly during transitions of care between the hospital and outpatient setting?

Marini: Pharmacists are essential to the successful integration of menin inhibitors into clinical practice. First, they play a key role in identifying which patients are appropriate candidates for therapy and determining when a menin inhibitor should be incorporated into the treatment plan.

In addition, these agents have unique toxicity profiles, and pharmacists are uniquely positioned to help monitor for and manage these adverse effects. Their expertise is critical for recognizing toxicities early, implementing supportive care strategies, and making treatment recommendations that allow patients to remain on therapy safely and effectively.

Ultimately, pharmacists contribute to both treatment selection and toxicity management, helping to ensure that patients derive the greatest possible benefit from menin inhibitor therapy.

Pharmacy Times: As experience with menin inhibitors continues to grow, what unanswered questions remain regarding treatment sequencing, combination approaches, or long-term outcomes, and what additional data would help inform future practice?

Marini: There are still many unanswered questions regarding menin inhibitors. Most of the available studies are single-arm trials, so it remains unclear how outcomes with these agents compare with those achieved using more traditional treatment approaches.

Another important unanswered question is how these therapies should be used in clinical practice. Should menin inhibitors be administered as single agents, or should they be combined with hypomethylating agents and venetoclax or with intensive chemotherapy? At this point, there is still considerable uncertainty regarding the optimal treatment strategy.

There are many unanswered questions in this space, and future clinical trials will provide important insights into how these agents should be incorporated into AML treatment paradigms.