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Nilotinib combined with multi-agent chemotherapy in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center prospective study with long-term follow-up

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Abstract

The aim of this study is to investigate the efficacy and safety of nilotinib combined with multi-agent chemotherapy in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Thirty patients with Ph+ ALL were recruited. Standard induction chemotherapy was given for 4 weeks. Nilotinib was administered beginning on day 15 of induction. After achieving hematologic complete remission (HCR), patients received either seven courses of consolidation or hematopoietic cell transplantation (HCT). Nilotinib was continued 2 years after achieving HCR or before stem cell transplantation conditioning. HCR and molecular complete response (MCR), overall survival (OS), hematologic relapse-free survival (HRFS), molecular relapse-free survival (MRFS), toxicity, and nilotinib levels in the serum and cerebrospinal fluid were evaluated. All patients achieved HCR, and cumulative MCR rate was 83.3%. The median HRFS and OS were 18 and 47.5 months, respectively. Four-year HRFS and OS rates were 54% and 45%, respectively. The median MRFS and 4-year MRFS for the patients with MCR were 19 months and 45%, respectively. The molecular response of patients after induction cycle had no impact on HRFS, MRFS, or OS. The patients who achieved MCR after 3 and 6 months had superior HRFS. The HCT cohort in the first HCR had significantly lower rates of relapse and longer MRFS, HRFS, and OS. Most adverse events were reversible with dose reduction or transient interruption of nilotinib therapy. Only traces of nilotinib were detected in cerebrospinal fluid. Nilotinib combined with cytotoxic chemotherapy was effective and translated to a high HCR and MCR for patients with Ph+ ALL. It should be noted that nilotinib cannot cross the blood–brain barrier.

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Acknowledgements

The authors thank all the doctors and nurses in the Leukemia Center for their professional assistance.

Funding

This work was supported by the State Key Program of National Natural Science of China (81430004), the Tianjin Clinical Research Center for Blood Diseases (15ZXLCSY00010), the National Natural Science of China (81670159), and the Natural Science Foundation of Tianjin (15JCYBJC25700, 15JCYBJC25000).

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  1. Luekemia Center, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Science, Tianjin, 300020, China

    Bingcheng Liu, Ying Wang, Chunlin Zhou, Hui Wei, Dong Lin, Wei Li, Kaiqi Liu, Guangji Zhang, Shuning Wei, Yan Li, Benfa Gong, Yuntao Liu, Xiaoyuan Gong, Yingchang Mi & Jianxiang Wang

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The patients provided the required written informed consent. All procedures were conducted according to the Declaration of Helsinki. The study was approved by the local ethics committee of the Chinese Academy of Medical Sciences and Blood Diseases Hospital (Approval Number: YL2011032201). This trial was registered as ChiCTR-ONC-12002469.

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Liu, B., Wang, Y., Zhou, C. et al. Nilotinib combined with multi-agent chemotherapy in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center prospective study with long-term follow-up. Ann Hematol 98, 633–645 (2019). https://doi.org/10.1007/s00277-019-03594-1

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