Abstract Background Infantile LGGs are a challenge to manage because of acute illness at presentation and unpredictable response to standard LGG chemotherapy. Methods We present 3 cases of infants with LGG (ages 4, 6, and 12 months) treated with mirdametinib, a selective MEK1/2 inhibitor with high blood-brain barrier penetration. Results All 3 cases were diagnosed with KIAA1549::BRAF fusion-positive pilocytic astrocytoma. Symptoms for all patients corresponded to tumor location (1 brainstem, 2 suprasellar optic pathway gliomas OPG) and included failure to thrive and regression of milestones. All were treated with mirdametinib at 3mg/m2 BID daily (2 first-line and 1 second-line). Overall, treatment was well tolerated, with expected grade 1-2 CPK elevations and grade 1 rash in all patients. One patient required a dose reduction due to neck weakness. The patient with a non-enhancing brainstem tumor had a minor response at 2 months (-32%), and a partial response at 4 months (-55%) that was sustained at 6 months (-63%) by RAPNO criteria. One with OPG had stable disease over 4 months with an incremental decrease in size 2 (-9%) and 4 (-18%) months, and a gradual reduction in tumor enhancement. The second OPG, who had only one disease evaluation after 2 months on MEKi, showed an increase in tumor volume that could be confounded by a 2-week delay between the baseline evaluation and treatment initiation, but with a marked decrease in tumor enhancement. All the infants showed significant improvement in their neurological status, and this improvement was sustained through their most recent follow-up. Supportive care medications were weaned for all 3 patients, and all remain on treatment. Conclusion In the short term, mirdametinib was well tolerated by 3 infants. Two showed progressive reduction in tumor volume, and one showed sustained partial response. More longitudinal follow-up and patients are needed to better report the safety and efficacy of mirdametinib in infants.
Bagchi et al. (Tue,) studied this question.