Frontline combination of dasatinib and low-intensity chemotherapy in adults with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia

ABSTRACT

Background

Studies on dasatinib-based low-intensity induction regimens and post-remission strategies are limited in China. Therefore, we conducted a single-center phase 2 trial in newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) to establish the efficacy and safety of this treatment approach.

Research design and methods

Patients received one month of dasatinib plus low-intensity chemotherapy and two months of dasatinib monotherapy for induction, followed by a single course of high-dose methotrexate for consolidation. Subsequently, they underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) or tyrosine kinase inhibitor (TKI)-based treatment for maintenance therapy between October 2015 and August 2022.

Results

Twenty-two patients were enrolled. Median age was 45 years (range, 20–71). The rates of major and complete molecular responses in the third month were 18.2% and 40.9% respectively. With a median follow-up of 15 months (range, 5–89), the estimated 3-year disease-free survival (DFS) and overall survival (OS) were 52.4% and 73.2%, respectively. The TKI-based cohort had a significantly poorer DFS (p = 0.014) and OS (p = 0.008) than the allo-HSCT cohort.

Conclusions

Our results suggest that dasatinib-based low-intensity chemotherapy is safe and effective as an induction strategy in the Chinese population. Allo-HSCT plays a crucial role in the long-term outcomes of patients with Ph+ ALL.

Clinical trial registration

The trial was registered at ClinicalTrials.gov as NCT02690922.

KEYWORDS:

• Acute lymphoblastic leukemia
• allogeneic stem cell transplantation
• dasatinib
• Philadelphia chromosome positive
• tyrosine kinase inhibitors

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial relationships or otherwise to disclose.

Author contributions

Z Hong, L Meng and Z Han conceived and designed the study. Y Peng, J Huang, J Yin, F Meng, Y Cao, L Huang, D Li, Y Zhang, D Zhang, L Meng and Z Hong treated patients enrolled and provided clinical data. Y Peng collected and analyzed the data and produced tables and figures. Y Peng and J Huang were involved in data interpretation and manuscript writing. All authors reviewed and revised the manuscript and approved the final version for publication.

Acknowledgments

The authors would like to thank all the participating patients and their families.

Ethical approval

The study was reviewed and approved by the institutional review board of the Medical Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (TJ-IRB20160403).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant Nos. 81873430, 81974414 and 81772788] and Natural Science Foundation of Hubei Province (General Program) [Grant No. 2020CFB432].