Potential of ponatinib to treat chronic myeloid leukemia and acute lymphoblastic leukemia

Figures & data

Table 1 Clinical characteristics of patients at baseline

	Chronic phase CML (n = 43)	Accelerated phase CML (n = 9)	Blast phase CML (n = 8)	Ph-positive ALL (n = 5)
Age in years (range)	55 (27–85)	61 (42–77)	51 (26–73)	36 (27–67)
Sex
Male	21 (49%)	6 (67%)	5 (62%)	5 (100%)
Female	22 (51%)	3 (33%)	3 (38%)	0
Median time from diagnosis to treatment years (range)	6.6 (0.8–23.5)	6.7 (2.7–16.2)	6.5 (1.6–19.8)	1.2 (0.8–1.9)
Hematologic analysis (values are × 10^−3/mm^3)
Median white-cell count (range)	5.8 (0.6–65.2)	27.9 (1.6–212.7)	9.5 (1.5–36.9)	14.9 (0.2–92.7)
Median platelet count (range)	217.5 (28–900)	224.0 (28–1400)	22.0 (13–172)	14.0 (7–71)
Previous use of tyrosine kinase inhibitors
≥2 drugs	42 (98%)	9 (100%)	8 (100%)	2 (40%)
≥3 drugs	27 (63%)	8 (89%)	6 (75%)	0

Abbreviations: CML, chronic myeloid leukemia; ALL, acute lymphoblastic leukemia.

Table 2 Response from ponatinib treatment: Phase I trial data

	Chronic phase CML (n = 43)		Accelerated phase CML, blast phase CML, and Ph+ ALL (n = 22)
	All patients (n = 43)	T3151 mutation (n = 12)	All patients (n = 22)	T3151 mutation (n = 7)
CCyR	27 (63%)	9 (75%)	3 (14%)	1 (14%)
MCyR	31 (72%)	11 (92%)	7 (32%)	2 (29%)
CHR	42 (98%)	12 (100%)	N/A	N/A
MaHR	N/A	N/A	8 (36%)	2 (29%)
MMR	19 (44%)	8 (67%)	2 (9%)	2 (29%)

Abbreviations: CCyR, complete cytogenetic response; CHR, complete hematologic response; CML, chronic myeloid leukemia; MaHR, major hematologic response; MCyR, major cytogenetic response; MMR, major molecular response; N/A, not available; Ph+ ALL, Philadelphia chromosome positive acute lymphoblastic leukemia.

Table 3 Response rates from PACE (ponatinib Ph+ ALL and CML evaluation)

CP-CML	Overall (n = 267)	Resistant/intolerant (n = 203)	T315I (n = 64)
MCyR % (95% CI)	54% (48–60)	49% (42–56)	70% (58–81)
Median time to MCyR (range)	84 days (49–334 days)	N/A	N/A
CCyR % (95% CI)	44% (38–50)	37% (31–44)	66% (52–77)
AP-CML	Overall (n = 83)	Resistant/intolerant (n = 65)	T315I (n = 18)
MaHR % (95% CI)	52% (41–63)	55% (43–68)	39% (17–64)
Median time to MaHR (range)	21 days (12–176 days)	N/A	N/A
Median duration of MaHR (range)	9.5 months (1.1–17.7 months)	N/A	N/A
CHR % (95% CI)	44% (33–55)	45% (32–57)	39% (17–64)
BP-CML	Overall (n = 62)	Resistant/intolerant (n = 38)	T315I (n = 24)
MaHR % (95% CI)	31% (20–44)	32% (18–42)	29% (13–51)
Median time to MaHR (range)	29 (12–113 days)	N/A	N/A
Median duration of MaHR (range)	4.7 months (1.8–14.1+ months)	N/A	N/A
CHR % (95% CI)	21% (12–33)	24% (11–40)	17% (5–37)
Ph+ ALL	Overall (n = 32)	Resistant/intolerant (n = 10)	T3151 (n = 22)
MaHR % (95% CI)	41% (24–59)	50% (19–81)	36% (17–59)
Median time to MaHR (range)	20 (11–168 days)	N/A	N/A
Median duration of MaHR (range)	3.2 months (1.8–8.8+ months)	N/A	N/A
CHR % (95% CI)	34% (19–53)	40% (12–74)	32% (14–55)

Abbreviations: AP-CML, accelerated phase CML; BP-CML, blast phase CML; CCyR, complete cytogenetic response; CHR, complete hematologic response; CI, confidence interval; CML, chronic myeloid leukemia; MaHR, major hematologic response; MCyR, major cytogenetic response; Ph+ ALL, Philadelphia chromosome positive acute lymphoblastic leukemia; CP, chronic phase.