Olverembatinib (HQP1351)-based therapy in adults with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia: results of a real-world study

Ziyu Wen¹Zhi Liu²XU YE³Zhiping Fan¹Ren Lin¹Fen Huang¹Li Xuan¹Xiaofang Li¹Hua Jin¹Min Dai¹Jing Sun¹Xuan Zhou¹Qiang Wang¹Xiaoli Liu¹Hongsheng Zhou^1*Na Xu^1*

• ¹Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
• ²Department of Hematology, Guangdong Second Provincial General Hospital, Guangzhou, China
• ³Department of Gastroenterology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

Background: Relapsed or refractory Philadelphia chromosome positive acute lymphoid leukemia (R/R Ph + ALL) and chronic myeloid leukemia blast phase (CML-BP) usually have dismal outcomes. Olverembatinib (HQP1351) is a novel, yet-to-be-widely-used thirdgeneration tyrosine kinase inhibitor (TKI) that has shown promising preliminary efficacy and safety in clinical trials against nearly all BCR-ABL1 kinase mutations, including T315I. Methods: Date were respectively collected and analyzed to explore the efficacy and safety of olverembatinib-based therapy for advanced Ph + leukemia. The major outcome was overall response rate at 28 days. Secondary outcomes included overall survival (OS), event-free survival (EFS) and disease-free survival (DFS), the proportion of patients undergoing allo-HSCT and adverse events. Results: Participants included 59 patients (40 with Ph + ALL and 19 with CML-BP), of whom 36 (61.0%) patients were male and 23 (39.0%) were female. The median (IQR) age was 39 (30-48) years and the median (IQR) duration of follow-up was 7.8 (4.1-11.3) months. A total of 16 (27.1%) and 11 (18.6%) patients had been treated with 2 and ≥ 3 prior TKIs, respectively; 19 (33.9%) patients had received ponatinib. Of 19 CML patients, 12 (63.2%) patients reached CR/CRi by day 28, 5 (26.3%) patients attained complete cytogenetic response with a median time of 2.9 months and 2 (10.5%) patients attained major molecular response with a median time of 5.5 months. A total of 40 ALL patients, 37 (92.5%) achieved CR/CRi by day 28, and 30 (75%) attained measurable residual disease negativity; while 22 (55.0%) reached complete molecular response. The probabilities of disease-free survival, event-free survival, and overall survival at 12 months were 80.3% (95% CI, 61.0%-90.7%), 80.2% (95% CI, 61.0%-90.7%), and 93.3% (95% CI, 75.8%-98.3%), respectively in patients with R/R Ph + ALL and 52.0% (95% CI, 17.7%-78.0%), 36.6% (95% CI, 9.5%-65.0%), and 75.6% (95% CI, 37.7%-92.3%), respectively in those with CML-BP. The most common treatment-associated non-hematologic adverse events, classified as grade 1/2, encompassed skin hyperpigmentation, proteinuria, elevated liver enzyme levels, and hypertriglyceridemia. Conclusions: Olverembatinib-based therapy demonstrated strong efficacy and an predictable toxicity in patients with advanced Ph + leukemia.