Managing side effects of menin inhibitors in clinical practice

The AML Hub was pleased to speak with Gail Roboz, Weill Cornell Medicine, New York, US. We asked, What side effects are typically observed with menin inhibitor-based regimens, and how do you approach managing them in clinical practice?

Roboz provides an overview of the key toxicities associated with menin inhibitor regimens in the treatment of NPM1-mutated (NPM1m) and KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML), including differentiation syndrome (DS), QT prolongation, and drug–drug interactions. She highlights the importance of recognizing these side effects as menin inhibitors move into routine clinical practice and shares how she approaches managing them.

Key points

• Two menin inhibitors, revumenib and ziftomenib, are currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of genetically defined relapsed or refractory acute leukemias.^1,2 Revumenib is approved for KMT2Ar and NPM1m disease, whereas ziftomenib is approved for NPM1m AML.^1,2 Several additional menin inhibitors remain under investigation in clinical trials.³
• With the increasing use of menin inhibitors for the treatment of AML, the potential for toxicity is a key consideration for clinical practice.
• DS is a key and potentially life-threatening toxicity associated with menin inhibitors. Clinical features may include fever, respiratory distress, pleural or pericardial effusions, peripheral edema, hypotension, weight gain, renal dysfunction, and pulmonary infiltrates.^1,2
  • Diagnosis of DS can be challenging, as its features can mimic those of other AML-related complications such as pneumonia or sepsis.
  • As with DS management in acute promyelocytic leukemia, early initiation of corticosteroids (e.g. dexamethasone) is critical when DS is suspected in AML.
  • Interruption of menin inhibitor therapy should be avoided, if possible, to preserve anti-leukemic efficacy.
• QT interval prolongation is another important safety concern with menin inhibitors, particularly in patients receiving additional medications that may contribute to QT prolongation, such as antiemetics or antibiotics.^1,2
  • Baseline and ongoing electrocardiographic monitoring is required to detect QT prolongation during treatment.
• Drug–drug interactions, especially with antifungals and other commonly used AML therapies, necessitate careful monitoring throughout menin inhibitor treatment and potential dose adjustments.^1,2
• Awareness of other potential toxicities associated with menin inhibition, such as nausea, gastrointestinal toxicities and myelosuppression, is also important for optimal management.^1,2
• Menin inhibitors are emerging as a key therapeutic strategy in AML, and awareness and optimal management of associated toxicities will be critical to their use in clinical practice.

This educational resource is independently supported by Kura Oncology. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence.