Table 1.

Longitudinal mutation status of patients with low-level mutations detected by MS at baseline

Pt ID	Disease phase at study entry	Number of prior TKIs	Mutation history*	Mutation status by Sanger sequencing at baseline	Low-level mutations at baseline†	Months on ponatinib	Outcome	Mutation status by Sanger sequencing at treatment failure or discontinuation (%)‡
109	CP-CML	3	No mutation detected	No mutation detected	E459K	4.2	Discontinued therapy§	Not evaluable
210	CP-CML	3	E255K	E255K	G250E	10.7	Discontinued therapy§	Not evaluable
239	CP-CML	3	M244V, E255K, T315I	E255K, T315I	M244V	17.6	Discontinued therapy‖	Not evaluable
288	CP-CML	2	T315I	No mutation detected	T315I	21.9	Discontinued therapy‖	T315I (20)
35	CP-CML	2	No mutation detected	No mutation detected	F359V	31.0	Maintained MCyR	No mutation detected
45	CP-CML	2	E255K, T315I	E255K	E255V, T315I	24.8	Maintained MCyR
215	CP-CML	3	T240M, E255V, T315I	T315I	E255V	30.7	Maintained MCyR
271	CP-CML	1	G250E, T315I	G250E, E255V	M244V, Y253H	26.3	Maintained MCyR
253	CP-CML	2	F317L	F317L	F317L¶	27.8	Maintained MMR
314	CP-CML	1	T315I	No mutation detected	M244V, G250E, F359I	28.3	Maintained MMR
358	CP-CML	3	Y253F, D276G	Y253F	Q252H, T315I	28.5	Maintained MMR
361	CP-CML	3	M244V, F359V	F359V	E355G	28.2	Maintained MMR
365	CP-CML	2	T315I, F359V	F359V	T315I	28.4	Maintained MMR
255	CP-CML	1	T315I	T315I	F317L	22.1	Lost MMR
381	CP-CML	1	No mutation detected	No mutation detected	E255K	25.8	Lost MMR
216	CP-CML	2	E355A, T315I	E355A	T315I	30.7	No MCyR	T315I, E355A (10, 10)
19	CP-CML	4	M351T, F359V	F317L, E450G	F359V	29.6	Progressive disease	F317L, E450G (10, 10)
26	CP-CML	3	V299L	V299L	E255K, F317L	32.2	Progressive disease	E255K (70)
47	CP-CML	2	T315I, F317L	T315I	F317L	3.1	Progressive disease	T315I (100)
96	CP-CML	3	T315I, F359C	T315I, F359C	V299L	0.9	Progressive disease	Not evaluable
97	CP-CML	3	No mutation detected	No mutation detected	F317L	0.9	Progressive disease	Not evaluable
153	CP-CML	3	No mutation detected	No mutation detected	T315I	8.2	Progressive disease	No mutation detected
168	CP-CML	3	T315I	T315I	F317L	3.9	Progressive disease	T315I (100)
228	CP-CML	2	T315I, F317L	T315I, F317L	F317L¶	8.0	Progressive disease	T315I (100)
258	CP-CML	4	M244V, F359V	F359V	M244V	7.3	Progressive disease	Y253H, F359V (100, 100)
281	CP-CML	3	G250E	No mutation detected	G250E	18.9	Progressive disease	G250E (20)
348	CP-CML	2	Y253H, F317L, H396R	F317L, H396R	G250E, T315I	2.7	Progressive disease	F317L, H396R (60, 20)
389	CP-CML	3	T315I, F359V	F359V	E255K, T315I	7.4	Progressive disease	T315I (100)
83	AP-CML	3	Y253F, E255K, T315I	T315I	Y253F, E255K	2.1	Discontinued therapy‖	T315I (50)
150	AP-CML	3	E355G, L248V	L248V	E355G	27.5	Maintained MMR
292	AP-CML	1	M244V, T315I	M244V, T315I	F359I	29.2	Lost MMR	T315I (50)
331	AP-CML	3	T315I, F317L, H396R	H396R	F317L	28.4	No MCyR	H396R (50)
127	AP-CML	2	T315I	T315I	E255V	24.8	Progressive disease	Not evaluable
130	AP-CML	2	T315I	No mutation detected	T315I	2.4	Progressive disease	Not evaluable
143	AP-CML	2	T315I	No mutation detected	F317L	20.0	Progressive disease	Not evaluable
208	AP-CML	2	T315I	T315I	E255V, H396R	6.2	Progressive disease	T315I (100)
278	AP-CML	2	T315I, F359C	F359C	T315I	31.0	Progressive disease	Not evaluable
290	AP-CML	3	T277A, F317L, M351T, L387F	L387F	F317L	30.9	Progressive disease	Not evaluable
301	AP-CML	2	T315I	No mutation detected	T315I	28.6	Progressive disease	Not evaluable
332	AP-CML	3	No mutation detected	No mutation detected	T315I	28.4	Progressive disease	Not evaluable
37	BP-CML	2		T315I	E255K	3.2	Discontinued therapy#	T315I (100)
4	BP-CML	2	T315I	T315I	V299L, F317L	1.8	Progressive disease	T315I (100)
163	BP-CML	2	T315I, F359V	T315I, F359V	F317L	1.2	Progressive disease	T315I, F359V (100, 100)
1	BP-CML	3		No mutation detected	L248V, G250E, Q252H, F317L, F359V	0.2	Death	No mutation detected
66	BP-CML	2	T315I	E255K, T315I	E255V	0.7	Death	Not evaluable
77	BP-CML	3	No mutation detected	E255K	E255V, T315I	0.0	Death	Not evaluable
88	BP-CML	3	E255K	E255K	E255V	2.9	Death	E255K, E255V (20, 20)
252	BP-CML	2	M244V, F317L	M244V, F317L	F317L¶	12.5	Death	Not evaluable
3	Ph+ ALL	2		F317I	V299L	5.6	Progressive disease	E255V, F317I (100, 100)
93	Ph+ ALL	3	T315I	T315I	M351T	3.8	Progressive disease	Not evaluable
144	Ph+ ALL	2	No mutation detected	E255V, T315I	Q252H ×2, V299L ×2, F317L ×2	1.0	Progressive disease	E255V, T315I (100, 60)
171	Ph+ ALL	3	G250E, F317L	G250E, F317L	T315I, F359V	7.5	Progressive disease	G250E, Y253H, E255V, T315I, F317L (10, 40, 10, 30, 100)
167	Ph+ ALL	2	T315I	No mutation detected	Y253H, T315I	15.5	Death	Not evaluable

^*Mutation analysis performed by Sanger sequencing. Mutations detected at low levels at baseline are underlined.

^†Low-level mutations detected by MS alone (present below the detection limit of Sanger sequencing, ∼10%). Of the mutations detected by Sanger sequencing and included in the MS assay design, all except 6 were detected.

^‡Percent mutant at therapy failure/discontinuation estimated by Sanger sequencing, mutations detected at low levels at baseline are underlined; mutations not detected at baseline by either method (“new mutations”) are bold.

^§Reason for discontinuation: withdrawal by subject (n = 2).

^‖Reason for discontinuation: adverse event (n = 3).

^¶MS detected 2 different nucleotide substitutions that both resulted in an F317L mutation in these samples, only 1 of which was also detected by Sanger sequencing.

^#Reason for discontinuation: other (n = 1).