Mechanism of early resistance

Early resistance: 20% of all patients.

Seen with all mutations, but most often with KIT exon 9, PDGFRA, and WT. Primary mutations in KIT exon 13 and 17 are rare and response noted in exon 13 (K642E) but resistant with V654A.

PDGFRA mutations are rare, and definite conclusions regarding response to imatinib are difficult to make. PDGFRA mutations are rare, and exon 12 and 14 are sensitive while D842 V PDGFRA mutations are resistant (rare exceptions).

Level of plasma imatinib level may correlate with early resistance.