A recent case study indicates that gilteritinib, a targeted treatment primarily used as a FLT3 inhibitor, may also be effective as an anaplastic lymphoma kinase (ALK) inhibitor in acute myeloid leukemia (AML). The findings, detailed in NPJ Precision Oncology, suggest a potential new treatment avenue for AML patients with specific genetic mutations.
The case study focused on a 75-year-old woman with ALK-fusion positive AML and a suspected germline DDX41 mutation. The patient had previously undergone standard therapies without sustained improvement, remaining transfusion-dependent with worsening disease. Treatment with gilteritinib led to significant improvements, with near-normal blood counts achieved within weeks and sustained for over a year.
Clinical Improvements with Gilteritinib
Within three weeks of initiating gilteritinib, the patient reported reduced fatigue, and subsequent lab work showed near-normalization of peripheral blood counts over the following eight weeks. By week ten, absolute neutrophil counts, hemoglobin levels, and platelet counts had begun to normalize. A bone marrow biopsy revealed no increase in blasts or abnormal monocytes, indicating a significant response to ALK inhibition.
"Our findings confirm that a RANBP2-ALK fusion can act as a driver mutation in AML and that gilteritinib can be a clinically effective and well-tolerated ALK inhibitor," the researchers stated. They suggest that gilteritinib could be considered as a component of treatment for any AML patient whose disease harbors an inv(2)(p23q13) mutation.
Context of ALK Inhibition in Cancer
ALK inhibitors like crizotinib, ceritinib, and alectinib are established treatments for non-small cell lung cancer (NSCLC), demonstrating improvements over chemotherapy. Alectinib recently received FDA approval for adjuvant treatment of NSCLC, showing a 94% 2-year overall survival rate compared to 64% with chemotherapy in the ALINA trial.
Despite the availability of other ALK inhibitors, gilteritinib was chosen due to insurance coverage feasibility and specific clinical considerations. The researchers emphasized the importance of compassionate use programs, particularly for rare cancers with rare, targetable genetic variations, where clinical trials and FDA approvals may be limited.
Challenges in Rare Cancer Treatment
The study also highlights the challenges in securing approval and insurance coverage for treatments targeting rare genetic variations in rare cancers. The authors noted that this often restricts the quality of options available to patients. The patient's history of essential thrombocytopenia (ET) and AML may be linked to her presumed germline DDX41 alteration, which, paradoxically, has been associated with more favorable survival in some cases.
