Table 3:

Targeted therapy used

Patient number	Disease	Target	Proposed drug or target/pathway inhibitor	Drug used	Tier	Toxicity attributed to targeted therapy	How targeted therapy was accessed?	Detected with NGS only
1	AML, new diagnosis	FLT3 ITD	FLT3 inhibitor	sorafenib	1	*	off label
121	AML, new diagnosis	FLT3 p.I836del	FLT3 inhibitor	sorafenib	3	none	off label	X
140	AML, new diagnosis	FLT3 ITD	FLT3 inhibitor	sorafenib	1	*	off label
15	AML, relapsed	FLT3 ITD	FLT3 inhibitor	gilteritinib	1	*	single patient IND (compassionate use)
31	AML, relapsed	NRAS	MEK inhibitor	trametinib	3	*	off label	X
66	AML, relapsed	BCR-ABL1	imatinib/dasatinib	dasatinib	2	*	off label
72	AML, relapsed	NRAS, PTPN11	MEK inhibitor	trametinib	3	none	off label	X
144	AML, relapsed	FLT3 ITD	FLT3 inhibitor	midostaurin, gilteritinib	1	*	off label (midostaurin); expanded access program (gilteritinib)
152	AML, relapsed	CSF3R	dasatinib	dasatinib	3	*	off label	X
18	B-ALL, refractory	EPOR-IGH	ruxolitinib	ruxolitinib	3	none	clinical trial (NCT02723994)	X
16	B-ALL, relapsed	NRAS	MEK inhibitor	everolimus	3			X
			mTOR inhibitor		5	none	off label
37	B-ALL, relapsed	NUP214-ABL1	imatinib/dasatinib	dasatinib	3	none	off label	X
38	B-ALL, relapsed	RCSD1-ABL2	imatinib/dasatinib	imatinib	3	*	off label	X
43	B-ALL, relapsed	NRAS, KRAS	MEK inhibitor	trametinib	3	none	off label	X
55	B-ALL, relapsed	ABL1 p.T315I	ponatinib	ponatinib	1	none	FDA authorized indication	X
153	B-ALL, relapsed	TCF3-HLF	venetoclax	venetoclax	3	*	off label
23	MPAL, refractory	NUP214-ABL1	imatinib/dasatinib	imatinib, dasatinib	3	*	off label	X

^*Please see full description of toxicity within the case vignettes in the supplementary data