Table 4.

Mutations that have been consistently reported in the literature to confer resistance to 2G TKIs, ponatinib and asciminib^a.

Mutations conferring resistance to dasatinib	V299L, T315I/A, F317L/V/I/C
Mutations conferring resistance to nilotinib	Y253H, E255K/V, T315I, F359V/I/C
Mutations conferring resistance to bosutinib	E255K, V299L, T315I
Mutations conferring resistance to ponatinib	T315M/L
Mutations conferring resistance to asciminibb	G109D, Y115N, M244V, V289I, A337V/T, E355G, F359V, E462K, G463D/S, P465S, V468F, S501R, I502L

^aCombinations of mutations in cis on the same BCR::ABL1 molecule (compound mutations) are likely to display peculiar resistance profiles, different to those the individual mutants would display if present in trans on different molecules (i.e., independent clones). However, the in vivo data needed to complement in vitro IC₅₀ predictions are scarce, so precise indications cannot be formulated. It is likely that the great majority of compound mutations will be resistant to imatinib and 2G TKIs. Some T315I-inclusive compound mutations have so far been reported in ponatinib-resistant patients [120, 132] and also in asciminib-resistant patients [140].

^bFor asciminib-resistant mutations, the list is provisional and includes mutations within and outside the TKD reported to have been selected in patients who failed asciminib in published clinical trials [136–139]. These patients had been pretreated with multiple TKIs and further data will be needed to compile a more robust list.