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Ref Type Journal Article
PMID (31689840)
Authors Abdou Y, Kapoor A, Hamad L, Ernstoff MS
Title Combination of pembrolizumab and imatinib in a patient with double KIT mutant melanoma: A case report.
Journal Vol Issue Date Pages Journal Short Title
Medicine 98 44 2019 Nov e17769 Medicine (Baltimore)
URL
Abstract Text The treatment of metastatic melanoma has been revolutionized in the past decade because of the development of immunotherapies and targeted therapies. Despite these developments, there is still an unmet clinical need for more advanced combination therapies for the subset of patients who remain resistant to immunotherapy or targeted therapy alone. To our knowledge, no reports have been published on combinations of PD-1 blockades and c-KIT inhibitors in melanoma patients. Furthermore, data are limited regarding the safety and efficacy of this combination in patients harboring KIT mutations.We report a case of an 82-year-old female with metastatic melanoma who was found to have double KIT mutations at V559 and N822I.She was treated with a combination of c-KIT inhibitor and PD-1 blockade after being resistant to anti-PD-1 monotherapy.Patient developed two episodes of grade 2 liver toxicity requiring treatment breaks followed by a dose reduction. Her transaminitis eventually resolved and patient remained on combination treatment for almost two years with good control of her disease prior to progression.Treatment options for patients who progress after PD-1 inhibitors are very limited; therefore, there is a high unmet clinical need for this patient population. Combining Imatinib with checkpoint inhibitors may be efficacious in patients with metastatic melanoma and KIT mutations. This novel combination can cause additional toxicities which seem to be overall manageable.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
KIT V559X KIT N822I melanoma predicted - sensitive Imatinib + Pembrolizumab Case Reports/Case Series Actionable In a clinical case study, addition of Gleevec (imatinib) to Keytruda (pembrolizumab) in a patient with metastatic melanoma harboring an unspecified KIT V559 mutation and a KIT N822I resulted in a complete remission after 6 months and the patient stayed on therapy for 2 years (PMID: 31689840). 31689840