Table 1

Details on response during nilotinib or dasatinib therapy of imatinib-resistant patients with multiple mutations detected by sensitive multiplex mass spectrometry at switchover (mutations were considered not clinically resistant to the inhibitor received by the patient)

Disease phaseNo. of mutations by mass spectrometryMutations by mass spectrometryTherapy receivedNew mutations by sequencing during nilotinib/dasatinib*Months to CCyRMonths to MMRFollow-up, mo
CP 2 M244V, H396R Dasatinib M244V No CCyR No MMR 7 
CP 2 M351T, H396R Dasatinib  24 No MMR 30 
CP 2 M244V, G250E Dasatinib  3 No MMR 18 
CP 2 G250E, E255K Dasatinib  3 11 24 
CP 2 G250E, M351T Dasatinib T315I No CCyR No MMR 18 
CP 3 Q252H, E255K, H396R Dasatinib T315I No CCyR No MMR 5 
CP 3 G250E, E355G, E459K Dasatinib G250E, F317L No CCyR No MMR 22 
CP 3 M244V, L248V, F359I Dasatinib V299L No CCyR No MMR 20 
CP 6 M244V, L248V, G250E, Y253H, M351T, E355G Dasatinib  6 9 12 
CP 8 L248V, G250E, E255V, M351T, F359V, H396R, E459K, F486S Dasatinib F317L × 3† No CCyR No MMR 10 
CP 2 M244V, F359I Nilotinib F359I No CCyR No MMR 12 
CP 2 V299L, F317L Nilotinib Q252H No CCyR No MMR 4 
CP 2 M244V, G250E Nilotinib  No CCyR No MMR 15 
CP 3 M351T, F486S, F317L Nilotinib F317L No CCyR No MMR 18 
CP 5 G250E, M351T, E355G, F359I, H396R Nilotinib G250E, F359I, H396R No CCyR No MMR 3 
AP 2 M244V, H396R Dasatinib  21 No MMR 21 
AP 2 G250E, H396R Dasatinib T315A No CCyR No MMR 16 
AP 2 H396R, E459K Dasatinib  No CCyR No MMR 12 
AP 2 Y253H, E255K Dasatinib T315I No CCyR No MMR 4 
AP 3 M244V, E355G, F359V Dasatinib M244V, T315I 3 No MMR 35 
AP 3 G250E, M351T, F359V Dasatinib F317L No CCyR No MMR 36 
AP 3 M244V, M351T, H396R Dasatinib  No CCyR No MMR 33 
AP 4 G250E, Y253F, M351T, H396R Dasatinib T240A‡, G250E No CCyR No MMR 5 
AP 4 Y253F, F359I, F359V, H396R Dasatinib T315I No CCyR No MMR 18 
AP 8 M244V, L248V, E255V, E279K, M351T, E355A, E459K, F486S Dasatinib L248V, T315I,E355A No CCyR No MMR 24 
AP 2 M351T, H396R Nilotinib Y253H, E255V No CCyR No MMR 18 
BC 2 F359V, H396R Dasatinib F317L No CCyR No MMR 8 
BC 2 Y253H, E459K Dasatinib T315I No CCyR No MMR 3 
BC 4 G250E, E279K, H396R, F486S Dasatinib F317L × 2§ No CCyR No MMR 8 
BC 9 M244V, L248V, G250E, Y253H, M351T, F359V, H396R, E459K, F486S Dasatinib F317L No CCyR No MMR 4 
BC 2 M244V, Q252H Nilotinib Y253H, E255K, F359V No CCyR No MMR 2 
BC 2 Y253F, F359I Nilotinib  No CCyR No MMR 3 
BC 2 V299L, F317I Nilotinib E255V No CCyR No MMR 2 
BC 2 M244V, D276G Nilotinib D276G, E255V No CCyR No MMR 5 
Disease phaseNo. of mutations by mass spectrometryMutations by mass spectrometryTherapy receivedNew mutations by sequencing during nilotinib/dasatinib*Months to CCyRMonths to MMRFollow-up, mo
CP 2 M244V, H396R Dasatinib M244V No CCyR No MMR 7 
CP 2 M351T, H396R Dasatinib  24 No MMR 30 
CP 2 M244V, G250E Dasatinib  3 No MMR 18 
CP 2 G250E, E255K Dasatinib  3 11 24 
CP 2 G250E, M351T Dasatinib T315I No CCyR No MMR 18 
CP 3 Q252H, E255K, H396R Dasatinib T315I No CCyR No MMR 5 
CP 3 G250E, E355G, E459K Dasatinib G250E, F317L No CCyR No MMR 22 
CP 3 M244V, L248V, F359I Dasatinib V299L No CCyR No MMR 20 
CP 6 M244V, L248V, G250E, Y253H, M351T, E355G Dasatinib  6 9 12 
CP 8 L248V, G250E, E255V, M351T, F359V, H396R, E459K, F486S Dasatinib F317L × 3† No CCyR No MMR 10 
CP 2 M244V, F359I Nilotinib F359I No CCyR No MMR 12 
CP 2 V299L, F317L Nilotinib Q252H No CCyR No MMR 4 
CP 2 M244V, G250E Nilotinib  No CCyR No MMR 15 
CP 3 M351T, F486S, F317L Nilotinib F317L No CCyR No MMR 18 
CP 5 G250E, M351T, E355G, F359I, H396R Nilotinib G250E, F359I, H396R No CCyR No MMR 3 
AP 2 M244V, H396R Dasatinib  21 No MMR 21 
AP 2 G250E, H396R Dasatinib T315A No CCyR No MMR 16 
AP 2 H396R, E459K Dasatinib  No CCyR No MMR 12 
AP 2 Y253H, E255K Dasatinib T315I No CCyR No MMR 4 
AP 3 M244V, E355G, F359V Dasatinib M244V, T315I 3 No MMR 35 
AP 3 G250E, M351T, F359V Dasatinib F317L No CCyR No MMR 36 
AP 3 M244V, M351T, H396R Dasatinib  No CCyR No MMR 33 
AP 4 G250E, Y253F, M351T, H396R Dasatinib T240A‡, G250E No CCyR No MMR 5 
AP 4 Y253F, F359I, F359V, H396R Dasatinib T315I No CCyR No MMR 18 
AP 8 M244V, L248V, E255V, E279K, M351T, E355A, E459K, F486S Dasatinib L248V, T315I,E355A No CCyR No MMR 24 
AP 2 M351T, H396R Nilotinib Y253H, E255V No CCyR No MMR 18 
BC 2 F359V, H396R Dasatinib F317L No CCyR No MMR 8 
BC 2 Y253H, E459K Dasatinib T315I No CCyR No MMR 3 
BC 4 G250E, E279K, H396R, F486S Dasatinib F317L × 2§ No CCyR No MMR 8 
BC 9 M244V, L248V, G250E, Y253H, M351T, F359V, H396R, E459K, F486S Dasatinib F317L No CCyR No MMR 4 
BC 2 M244V, Q252H Nilotinib Y253H, E255K, F359V No CCyR No MMR 2 
BC 2 Y253F, F359I Nilotinib  No CCyR No MMR 3 
BC 2 V299L, F317I Nilotinib E255V No CCyR No MMR 2 
BC 2 M244V, D276G Nilotinib D276G, E255V No CCyR No MMR 5 

CCyR indicates complete cytogenetic response; MMR, major molecular response; CP, chronic phase; AP, accelerated phase; and BC, blast crisis.

*

Mutations became detectable by sequencing during nilotinib or dasatinib therapy. Mutations are coded according to the inhibitor received. Underlined mutations do not confer clinical resistance to the inhibitor received and were detected by mass spectrometry at switchover. Mutations in bold confer clinical resistance to the inhibitor received and were not detected at switchover by mass spectrometry.

†

Three different F317L mutations were acquired in this patient (c.949T > C, c.951C > G, and c.951C > A).

‡

Mutation not included in the design of the mass spectrometry assay.

§

Two different F317L mutations were detected in this patient (c.949T > C and c.951C > A).

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