Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial

Jiang, Qian; Li, Zongru; Qin, Yazhen; Li, Weiming; Xu, Na; Liu, Bingcheng; Zhang, Yanli; Meng, Li; Zhu, Huanling; Du, Xin; Chen, Suning; Liang, Yang; Hu, Yu; Liu, Xiaoli; Song, Yongping; Men, Lichuang; Chen, Zi; Niu, Qian; Wang, Hengbang; Lu, Ming; Yang, Dajun; Zhai, Yifan; Huang, Xiaojun

doi:10.1186/s13045-022-01334-z

Table 4 Multivariate analysis results of variables associated with treatment responses

From: Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial

	MCyR		CCyR		MMR		MR^4.0		MR^4.5
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
In 164 evaluable patients
Baseline BCR-ABL1 mutation status by Sanger sequencing		0.10		0.02		0.006		0.006		< 0.001
Single T315I mutation (ref.)
T315I + additional mutations	0.6 (0.3–1.0)	0.05	0.6 (0.3–1.1)	0.10	0.8 (0.4–1.3)	0.32	0.4 (0.2–1.0)	0.05	0.5 (0.2–1.1)	0.10
Other mutations	0.7 (0.5–1.2)	0.21	0.6 (0.3–1.0)	0.06	1.0 (0.5–1.8)	0.80	0.6 (0.3–1.3)	0.23	0.4 (0.1–1.6)	0.22
No mutation	0.6 (0.4–1.1)	0.13	0.5 (0.3–0.8)	0.009	1.0 (0.0–0.4)	< 0.001	0.1 (0.0–0.4)	0.005	0.0 (0.0–0.0)	< 0.001
Accelerated phase (ref. chronic phase)	0.5 (0.3–1.0)	0.04	0.5 (0.3–0.9)	0.03	0.6 (0.4–1.0)	0.06	0.7 (0.4–1.3)	0.29	0.8 (0.4–1.5)	0.51
Additional chromosomal abnormalities (ref. none)	0.7 (0.4–1.2)	0.18	0.7 (0.4–1.3)	0.23	0.7 (0.4–1.3)	0.24	0.8 (0.4–1.6)	0.49	0.6 (0.3–1.6)	0.33
Time from diagnosis to olverembatinib treatment, years (continuous)	0.9 (0. 9–1.0)	0.002	1.0 (0.9–1.0)	0.003	1.0 (0.9–1.0)	< 0.001	1.0 (0.9–1.0)	0.002	0.9 (0.8–1.0)	< 0.001
Number of prior TKIs (continuous)	0.8 (0.6–1.1)	0.16	0.7 (0.5–1.1)	0.10	0.7 (0.5–1.0)	0.03	0.7 (0.5–1.1)	0.12	0.8 (0.5–1.2)	0.27
Age (10 years)	0.9 (0.8–1.1)	0.36	0.8 (0.7–1.0)	0.07	0.9 (0.8–1.1)	0.30	0.9 (0.8–1.1)	0.44	1.0 (0.8–1.2)	0.90
In 118 evaluable patients
Baseline BCR-ABL1 mutation status by next-generation sequencing		0.31		0.13		0.002		< 0.001		< 0.001
Single T315I mutation (ref.)
T315I + additional mutations	0.6 (0.3–1.2)	0.15	0.7 (0.3–1.4)	0.26	0.4 (0.1–0.9)	0.03	0.5 (0.2–1.2)	0.13	0.7 (0.3–1.5)	0.35
Other mutations	0.7 (0.4–1.5)	0.40	0.6 (0.3–1.2)	0.14	0.8 (0.4–1.9)	0.67	0.7 (0.3–1.6)	0.42	0.5 (0.1–1.9)	0.29
Compound mutations	0.6 (0.3–1.2)	0.13	0.7 (0.3–1.4)	0.26	0.6 (0.3–1.2)	0.16	0.3 (0.1–1.1)	0.07	0.4 (0.1–1.2)	0.11
No mutation	0.7 (0.3–1.2)	0.15	0.5 (0.3–0.9)	0.02	0.0 (0.0–0.2)	< 0.001	0.0 (0.0–0.0)	< 0.001	0.0 (0.0–0.0)	< 0.001
Accelerated phase (ref. chronic phase)	0.8 (0.7–1.0)	0.10	0.8 (0.6–1.0)	0.03	0.9 (0.7–1.1)	0.21	0.9 (0.7–1.1)	0.45	1.0 (0.8–1.3)	0.82
Additional chromosomal abnormalities (ref. none)	0.3 (0.2–0.7)	0.004	0.4 (0.2–0.8)	0.007	0.4 (0.2–0.8)	0.009	0.7 (0.3–1.4)	0.32	0.8 (0.4–1.7)	0.59
Time from diagnosis to olverembatinib treatment, years (continuous)	0.9 (0.8–1.0)	0.003	1.0 (0.8–1.0)	0.004	0.9 (0.8–1.0)	< 0.001	0.9 (0.8–1.0)	0.003	0.9 (0.8–1.0)	0.002
Number of prior TKIs (continuous)	0.7 (0.4–1.0)	0.03	0.6 (0.4–1.0)	0.02	0.6 (0.4–0.9)	0.01	0.7 (0.4–1.0)	0.08	0.8 (0.5–1.3)	0.33
Age (10 years)	0.8 (0.7–1.0)	0.10	0.8 (0.6–1.0)	0.03	0.9 (0.7–1.1)	0.21	0.9 (0.7–1.1)	0.45	1.0 (0.8–1.3)	0.82

MCyR major cytogenetic response, CCyR complete cytogenetic response; CI confidential interval, HR hazard ratio, MMR, major molecular response
MR^4.0 molecular response 4, MR^4.5 molecular response 4.5, ref. reference, TKI tyrosine kinase inhibitor

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