Background
Mutations poorly sensitive to imatinib | M237V, I242T, M244 V, K247R, L248V, G250E, G250R, Q252R, Q252H, Y253F, Y253H, E255K, E255V, E258D, W261L, L273M, E275K, E275Q, D276G, T277A, E279K, V280A, V289I, V289I, V289A, E292Q, E292V, I293V, L298V, F311L, F311I, T315I, F317L, F317V, F317I, F317C, Y320C, L324Q, Y342H, M343T, A344V, A350V, M351T, E355D, E355G, E355A, F359V, F359I, F359C, F359L, D363Y, L364I, A365V, A366G, L370P, V371A, E373K, V379I, A380T, F382L, L384M, L387F, L387V, M388L, H396R, H396P, H396A, A397P, S417F, S417Y, I418S, I418V, A433T, S438C, E450K, E450G, E450A, E450V, E453G, E453A, E453K, E453V, E453Q, E459K, E459V, E459G, E459Q, M472I, P480L, F486S |
Mutations poorly sensitive to dasatinib | V299L, T315I, T315A, F317L, F317V, F317I, F317C |
Mutations poorly sensitive to nilotinib | Y253H, E255K, E255V, T315I, F359V, F359I, F359C |
Mutations poorly sensitive to bosutiniba | E255V, E255K, V299L, T315I |
Mutations poorly sensitive to ponatinib | T315M, T315L |
Brief overview of NGS methodologies
Methods
Results
Indications for the use of NGS testing in chronic phase CML | |
- in patients with failurea response to TKI therapy, irrespective of the TKI | |
- in patients with warninga response to TKI therapy, irrespective of the TKI | |
Indications for the use of NGS testing before allogeneic stem cell transplant (allo-SCT) | |
- BCR-ABL1 KD mutation status by NGS testing before allo-SCT may provide useful information regarding when post-transplant TKI therapy should be reinstated. Patients who do not have BCR-ABL1 KD mutation results by NGS available at the time of transplant should be testedb | |
Indications for the use of NGS testing in advanced CML phases | |
- all patients with advanced phase (AP or BC) either at diagnosis or during therapy | |
Indications for the use of NGS testing after TKI therapy discontinuation | |
- in patients relapsing after a TFR attempt if they fail to re-achieve MMR within 3–6 months after TKI re-treatment |