Clinical Impact of Continuous Dasatinib Administration on the Prognosis of Patients With BCR::ABL1 Acute Lymphoblastic Leukemia: Result of the Prospective MRD2014 Study Conducted by Fukuoka Blood and Marrow Transplantation Group (FBMTG)

Koji Nagafuji¹, Yoshikiyo Ito², Toshihiro Miyamoto³, Tetsuya Eto⁴, Tomohiko Kamimura⁵, Koji Kato⁶, Yasuhiko Miyazaki⁷, Atsuhi Wake⁸, Kentaro Kohno⁹, Ken Takase¹⁰, Yutaka Imamura¹¹, Naoyuki Uchida¹², Kazuki Tanimoto¹³, Noriaki Kawano¹⁴, Toshiro Kurokawa¹⁵, Yukio Kondo¹⁶, Tomoaki Fujisaki¹⁷, Junichi Tsukada¹⁸, Koji Yonemoto¹⁹, Koichi Akashi⁶

Affiliations

¹ Division of Hematology & Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
² Department of Hematology, Imamura General Hospital, Kagoshima, Japan.
³ Hematology/Respiratory Medicine, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
⁴ Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
⁵ Department of Hematology, HaraSanshin General Hospital, Fukuoka, Japan.
⁶ Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan.
⁷ Department of Hematology, Oita Prefectural Hospital, Oita, Japan.
⁸ Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Kawasaki, Japan.
⁹ Department of Hematology and Oncology, Japan Community Health Care Organization Kyushu Hospital, Kitakyushu, Japan.
¹⁰ Department of Hematology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
¹¹ Division of Hematology, Our Lady of the Snow Social Medical Corporation St. Mary's Hospital, Kurume, Japan.
¹² Department of Hematology, Federation of National Public Service Personnel Mutual aid Associations Toranomon Hospital, Tokyo, Japan.
¹³ Department of Hematology and Oncology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
¹⁴ Department of Hematology, Miyazaki Prefectural Hospital, Miyazaki, Japan.
¹⁵ Department of Hematology, Toyama Red Cross Hospital, Toyama, Japan.
¹⁶ Department of Hematology, Toyama Prefectural Central Hospital, Toyama, Japan.
¹⁷ Department of Hematology, Matsuyama Red Cross Hospital, Matsuyama, Japan.
¹⁸ Department of Hematology, University of Occupational and Environmental Health, Kitakyushu, Japan.
¹⁹ Division of Biostatistics, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Nishihara, Japan.

PMID: 40052397
DOI: 10.1111/ejh.14407

Multicenter Study

Clinical Impact of Continuous Dasatinib Administration on the Prognosis of Patients With BCR::ABL1 Acute Lymphoblastic Leukemia: Result of the Prospective MRD2014 Study Conducted by Fukuoka Blood and Marrow Transplantation Group (FBMTG)

Koji Nagafuji et al. Eur J Haematol. 2025 Jun.

. 2025 Jun;114(6):1001-1010.

doi: 10.1111/ejh.14407. Epub 2025 Mar 7.

Authors

Affiliations

¹ Division of Hematology & Oncology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
² Department of Hematology, Imamura General Hospital, Kagoshima, Japan.
³ Hematology/Respiratory Medicine, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
⁴ Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
⁵ Department of Hematology, HaraSanshin General Hospital, Fukuoka, Japan.
⁶ Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan.
⁷ Department of Hematology, Oita Prefectural Hospital, Oita, Japan.
⁸ Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations, Toranomon Hospital, Kawasaki, Japan.
⁹ Department of Hematology and Oncology, Japan Community Health Care Organization Kyushu Hospital, Kitakyushu, Japan.
¹⁰ Department of Hematology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
¹¹ Division of Hematology, Our Lady of the Snow Social Medical Corporation St. Mary's Hospital, Kurume, Japan.
¹² Department of Hematology, Federation of National Public Service Personnel Mutual aid Associations Toranomon Hospital, Tokyo, Japan.
¹³ Department of Hematology and Oncology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
¹⁴ Department of Hematology, Miyazaki Prefectural Hospital, Miyazaki, Japan.
¹⁵ Department of Hematology, Toyama Red Cross Hospital, Toyama, Japan.
¹⁶ Department of Hematology, Toyama Prefectural Central Hospital, Toyama, Japan.
¹⁷ Department of Hematology, Matsuyama Red Cross Hospital, Matsuyama, Japan.
¹⁸ Department of Hematology, University of Occupational and Environmental Health, Kitakyushu, Japan.
¹⁹ Division of Biostatistics, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, Nishihara, Japan.

PMID: 40052397
DOI: 10.1111/ejh.14407

Abstract

Aim: To assess the efficacy of continuous dasatinib in improving outcomes for adult patients with BCR::ABL1 ALL.

Methods: The prospective, multicenter ALL/MRD2014 trial introduced a modified protocol compared to the MRD2008 trial, incorporating continuous dasatinib use and reduced chemotherapy intensity.

Results: Among the 164 adult ALL patients enrolled (2014-2019), 61 were Philadelphia-positive (Ph+) (median age 50 years; 38 males, 23 females). Post-induction, 96.7% achieved complete remission (CR). The 3-year event-free survival (EFS) and overall survival (OS) were 51% and 76%, respectively. Patients undergoing allo-HSCT in CR1 had improved outcomes, with a 3-year EFS of 64% and OS of 87%. MRD-negative patients before transplantation exhibited superior survival (EFS: 71% vs. 29%; OS: 94% vs. 57%). Comparison with the MRD2008 trial revealed similar outcomes, with the MRD2014 trial achieving a 3-year EFS of 51% and OS of 76% vs. 52% and 84% in MRD2008. Although not statistically significant, the MRD2014 trial showed trends of increased relapse (CIR: 39% vs. 26%, p = 0.305) and reduced non-relapse mortality (NRM: 10% vs. 21%, p = 0.181).

Conclusion: The ALL/MRD2014 trial underscores the importance of MRD status and allo-HSCT in Ph+ ALL. Continuous dasatinib-based regimens offer favorable outcomes in MRD-negative patients.

Trial registration: This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000012382.

Keywords: BCR::ABL1; Philadelphia chromosome; acute lymphoblastic leukemia; dasatinib; tyrosine kinase inhibitor.

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References

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1. S. Lee, Y. J. Kim, C. K. Min, et al., “The Effect of First‐Line Imatinib Interim Therapy on the Outcome of Allogeneic Stem Cell Transplantation in Adults With Newly Diagnosed Philadelphia Chromosome‐Positive Acute Lymphoblastic Leukemia,” Blood 105, no. 9 (2005): 3449–3457.

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Clinical Impact of Continuous Dasatinib Administration on the Prognosis of Patients With BCR::ABL1 Acute Lymphoblastic Leukemia: Result of the Prospective MRD2014 Study Conducted by Fukuoka Blood and Marrow Transplantation Group (FBMTG)

Affiliations

Clinical Impact of Continuous Dasatinib Administration on the Prognosis of Patients With BCR::ABL1 Acute Lymphoblastic Leukemia: Result of the Prospective MRD2014 Study Conducted by Fukuoka Blood and Marrow Transplantation Group (FBMTG)

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Abstract

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