Skip to main content

Advertisement

SpringerLink
Log in

Real-world treatment patterns and clinical outcomes in patients with AML in Japan who were ineligible for first-line intensive chemotherapy

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Acute myeloid leukemia (AML) predominantly affects elderly adults, and its prognosis worsens with age. Treatment options for patients in Japan ineligible for intensive chemotherapy include cytarabine/aclarubicin ± granulocyte colony-stimulating factor (CA ± G), azacitidine (AZA), low-dose cytarabine (LDAC), targeted therapy, and best supportive care (BSC). The country’s aging population and the evolving treatment landscape are contributing to a need to understand treatment pathways and associated outcomes. This retrospective chart review evaluated outcomes in patients across Japan with primary/secondary AML who were ineligible for intensive chemotherapy and began first-line treatment or BSC between 01/01/2015 and 12/31/2018. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and healthcare resource utilization (HRU). Of 199 patients (58% > 75 years), 121 received systemic therapy (38 CA ± G, 37 AZA, 7 LDAC, 39 other) and 78 received BSC. Median OS was 5.4, 9.2, 2.2, 3.8, and 2.2 months for CA ± G, AZA, LDAC, other systemic therapy, and BSC, respectively; median PFS was 3.4, 7.7, 1.6, 2.3, and 2.1 months, respectively. HRU rates were uniformly high, with > 80% patients hospitalized in each cohort. The poor clinical outcomes and high HRU among Japanese AML patients who are ineligible for intensive chemotherapy highlight an unmet need for novel therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data sharing statement

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (e.g., protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.

References

  1. Hou HA, Tien HF. Genomic landscape in acute myeloid leukemia and its implications in risk classification and targeted therapies. J Biomed Sci. 2020;27:81.

    Article  Google Scholar 

  2. Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021;11:41.

    Article  Google Scholar 

  3. National Cancer Institute. Cancer stat facts: leukemia—acute myeloid leukemia (AML) 2020 [Available from: https://seer.cancer.gov/statfacts/html/amyl.html.

  4. Cancer Information Service NCC, Japan. Chronic lymphocytic leukemia/small lymphocytic lymphoma. 2016. Available from: https://ganjoho.jp/public/cancer/CLL/.

  5. Yi M, Li A, Zhou L, Chu Q, Song Y, Wu K. The global burden and attributable risk factor analysis of acute myeloid leukemia in 195 countries and territories from 1990 to 2017: estimates based on the global burden of disease study 2017. J Hematol Oncol. 2020;13:72.

    Article  Google Scholar 

  6. Thein MS, Ershler WB, Jemal A, Yates JW, Baer MR. Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. Cancer. 2013;119:2720–7.

    Article  Google Scholar 

  7. Miyamoto K, Minami Y. Precision medicine and novel molecular target therapies in acute myeloid leukemia: the background of hematologic malignancies (HM)-SCREEN-Japan 01. Int J Clin Oncol. 2019;24:893–8.

    Article  Google Scholar 

  8. Palmieri R, Paterno G, De Bellis E, Mercante L, Buzzatti E, Esposito F, et al. Therapeutic choice in older patients with acute myeloid leukemia: a matter of fitness. Cancers (Basel). 2020. https://doi.org/10.3390/cancers12010120.

    Article  PubMed  PubMed Central  Google Scholar 

  9. National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Acute Myeloid Leukemia. 2020;2:2021.

    Google Scholar 

  10. Heuser M, Ofran Y, Boissel N, Brunet Mauri S, Craddock C, Janssen J, et al. Acute myeloid leukaemia in adult patients: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31:697–712.

    Article  CAS  Google Scholar 

  11. Kiyoi H, Yamaguchi H, Maeda Y, Yamauchi T. JSH practical guidelines for hematological malignancies, 2018: I. Leukemia-1. Acute myeloid leukemia (AML). Int J Hematol. 2020;111:595–613.

    Article  Google Scholar 

  12. Naoe T. Editors’ choice how to improve outcomes of elderly patients with acute myeloid leukemia: era of excitement. Nagoya J Med Sci. 2020;82:151–60.

    PubMed  PubMed Central  Google Scholar 

  13. Wei G, Ni W, Chiao JW, Cai Z, Huang H, Liu D. A meta-analysis of CAG (cytarabine, aclarubicin, G-CSF) regimen for the treatment of 1029 patients with acute myeloid leukemia and myelodysplastic syndrome. J Hematol Oncol. 2011;4:46.

    Article  CAS  Google Scholar 

  14. Minakata D, Fujiwara S, Ito S, Mashima K, Umino K, Nakano H, et al. A low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming regimen versus a daunorubicin plus cytarabine regimen as induction therapy for older patients with acute myeloid leukemia: a propensity score analysis. Leuk Res. 2016;42:82–7.

    Article  CAS  Google Scholar 

  15. Jin J, Chen J, Suo S, Qian W, Meng H, Mai W, et al. Low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor priming regimen versus idarubicin plus cytarabine regimen as induction therapy for older patients with acute myeloid leukemia. Leuk Lymphoma. 2015;56:1691–7.

    Article  CAS  Google Scholar 

  16. MHLW approval of Vidaza® (azacitidine) for the treatment of acute myeloid leukemia. [press release]. 2021.

  17. Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126:291–9.

    Article  CAS  Google Scholar 

  18. Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, et al. Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol. 2016;34:972–9.

    Article  Google Scholar 

  19. Ma E, Bonthapally V, Chawla A, Lefebvre P, Swords R, Lafeuille MH, et al. An evaluation of treatment patterns and outcomes in elderly patients newly diagnosed with acute myeloid leukemia: a retrospective analysis of electronic medical records from US community oncology practices. Clin Lymphoma Myeloma Leuk. 2016;16:625-36 e3.

    Article  Google Scholar 

  20. Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94:1127–38.

    Article  CAS  Google Scholar 

  21. DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133:7–17.

    Article  CAS  Google Scholar 

  22. Seymour JF, Dohner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer. 2017;17:852.

    Article  Google Scholar 

  23. Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30:2670–7.

    Article  CAS  Google Scholar 

  24. Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020;135:2137–45.

    Article  CAS  Google Scholar 

  25. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei A, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–29.

    Article  CAS  Google Scholar 

  26. Chen Y, Yang T, Zheng X, Yang X, Zheng Z, Zheng J, et al. The outcome and prognostic factors of 248 elderly patients with acute myeloid leukemia treated with standard-dose or low-intensity induction therapy. Medicine (Baltimore). 2016;95:e4182.

    Article  CAS  Google Scholar 

  27. Xu J, Lv TT, Zhou XF, Huang Y, Liu DD, Yuan GL. Efficacy of common salvage chemotherapy regimens in patients with refractory or relapsed acute myeloid leukemia: a retrospective cohort study. Medicine (Baltimore). 2018;97:e12102.

    Article  CAS  Google Scholar 

  28. Venclexta PI (Japanese label). 2021.

  29. Griffin JD, Yang H, Song Y, Kinrich D, Shah MV, Bui CN. Treatment patterns and healthcare resource utilization in patients with FLT3-mutated and wild-type acute myeloid leukemia: a medical chart study. Eur J Haematol. 2019;102:341–50.

    Article  CAS  Google Scholar 

  30. Miyamoto T, Sanford D, Tomuleasa C, Hsiao HH, Olivera LJE, Enjeti AK, et al. Real-world treatment patterns and clinical outcomes in patients with AML unfit for first-line intensive chemotherapy. Leuk Lymphoma. 2022. https://doi.org/10.1080/10428194.2021.2002321.

    Article  PubMed  Google Scholar 

  31. DiNardo CD, Pratz KW, Letai A, Jonas BA, Wei AH, Thirman M, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018;19:216–28.

    Article  CAS  Google Scholar 

  32. Miyawaki S. JSH guideline for tumors of hematopoietic and lymphoid tissues: leukemia 1. Acute myeloid leukemia (AML). Int J Hematol. 2017;106:310–25.

    Article  Google Scholar 

  33. Ito T, Sanford D, Tomuleasa C, Hsiao H-H, Enciso Olivera L, Enjeti A, et al. Patterns of healthcare resource utilization (HRU) in unfit patients with acute myeloid leukemia (AML) receiving first-line systemic treatment or best supportive care (BSC): a multicenter international study (CURRENT). Lawrenceville: ISPOR; 2021.

    Google Scholar 

  34. Stein EM, Bonifacio G, Latremouille-Viau D, Guerin A, Shi S, Gagnon-Sanschagrin P, et al. Treatment patterns, healthcare resource utilization, and costs in patients with acute myeloid leukemia in commercially insured and Medicare populations. J Med Econ. 2018;21:556–63.

    Article  Google Scholar 

Download references

Acknowledgements

Medical writing support was provided by Hayley Ellis, PhD, of Fishawack Communications Ltd, and funded by AbbVie.

Funding

AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.

Author information

Authors and Affiliations

  1. Department of Hematology, National Hospital Organization Mito Medical Center, Ibaraki-machi, Japan

    Chikashi Yoshida & Takuya Komeno

  2. Blood Disorders Center, Aiiku Hospital, Sapporo, Japan

    Takeshi Kondo & Akio Mori

  3. First Department of Internal Medicine, Kansai Medical University, Osaka, Japan

    Tomoki Ito & Atsushi Satake

  4. Department of Hematology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Masahiro Kizaki & Junichi Watanabe

  5. Department of Hematology, Okayama City Hospital, Okayama, Japan

    Kazuhiko Yamamoto

  6. Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Toshihiro Miyamoto

  7. Division of Hematology and Rheumatology, Department of Internal Medicine, Kindai University, Osaka, Japan

    Yasuyoshi Morita

  8. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Tetsuya Eto

  9. Department of Hematology, Sendai Medical Center, National Hospital Organization, Sendai, Japan

    Yuna Katsuoka

  10. Department of Hematology, Disaster Medical Center, Tokyo, Japan

    Naoki Takezako

  11. Department of Hematology, Kyoto Second Red Cross Hospital, Kyoto, Japan

    Nobuhiko Uoshima

  12. Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan

    Kazunori Imada

  13. Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan

    Jun Ando

  14. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yuichi Ishikawa & Hitoshi Kiyoi

  15. AbbVie GK, Tokyo, Japan

    Yoshiko Kawakami, Tetsuo Morita, Ikue Taneike & Masahiko Nakayama

  16. AbbVie, Inc., North Chicago, IL, USA

    Yinghui Duan & Cynthia Llamas

  17. AbbVie, Inc., Madrid, Spain

    Belen Garbayo Guijarro

  18. AbbVie, Inc., Singapore, Singapore

    Alexander Delgado

Authors
  1. Chikashi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takeshi Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomoki Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masahiro Kizaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuhiko Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Toshihiro Miyamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasuyoshi Morita
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tetsuya Eto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuna Katsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Naoki Takezako
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Nobuhiko Uoshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kazunori Imada
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jun Ando
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Takuya Komeno
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Akio Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yuichi Ishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Atsushi Satake
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Junichi Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Yoshiko Kawakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Tetsuo Morita
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Ikue Taneike
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Masahiko Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Yinghui Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Belen Garbayo Guijarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Alexander Delgado
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Cynthia Llamas
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Hitoshi Kiyoi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study conception and design: Yoshiko Kawakami, Tetsuo Morita, Ikue Taneike, Masahiko Nakayama, Yinghui Duan, Belen Garbayo Guijarro, Alexander Delgado, and Cynthia Llamas. Collection and assembly of data: All authors. Analysis and interpretation of data: All authors. Manuscript writing, editing, and approval: All authors.

Corresponding author

Correspondence to Chikashi Yoshida.

Ethics declarations

Conflict of interest

C. Yoshida: Investigator on AbbVie-funded clinical study. Honoraria from Bristol Myers Squibb, Novartis Pharma KK, Pfizer Japan Inc., Otsuka Pharmaceutical., AbbVie, Janssen Pharmaceutical KK, Nippon Shinyaku Co., Ltd., Chugai Pharmaceutical Co., Ltd. Research funding from Bristol Myers Squibb. T. Kondo: Advisory role for Astellas Pharma, Otsuka Pharmaceutical. Honoraria from Astellas Pharma, Bristol Myers Squibb, Otsuka Pharmaceutical, Novartis, and Sumitomo Dainippon Pharma. T. Ito: Research funding from AbbVie and Bristol Myers Squibb. Honoraria from AbbVie, Bristol Myers Squibb, Takeda Pharmaceutical Sanofi, CSL Behring, and Novartis. M. Kizaki, Y. Morita, T. Eto, Y. Katsuoka, N. Takezako, N. Uoshima, J. Ando, A. Mori, A. Satake, J. Watanabe: No potential conflicts of interest are reported. K. Yamamoto, T. Komeno: Investigator on AbbVie-funded clinical study. T. Miyamoto: Honoraria from AbbVie, Astellas Pharmaceutical, Astellas Amgen Pharmaceutical, Bristol Myers Squibb, Celgene, Merck Sharp & Dohme, Otsuka Pharmaceutical, and Takeda Pharmaceutical. K. Imada: Honoraria from Astellas Pharma, Bristol Myers Squibb, Celgene, Chugai Pharmaceutical, Kyowa Hakko Kirin, Nippon Shinyaku, Novartis, Otsuka Pharmaceutical, and Takeda Pharmaceutical. Y. Ishikawa: Personal fees from AbbVie, Astellas Pharma, Chugai Pharmaceutical, Daiichi-Sankyo, FUJIFILM, Kyowa Hakko Kirin, Nippon Shinyaku, Novartis, and Pfizer. Y. Kawakami, T. Morita, I. Taneike, M. Nakayama, Y. Duan, B. Garbayo Guijarro, A. Delgado, C. Llamas: Employees of AbbVie and may hold stock or options. H. Kiyoi: Research funding from AbbVie, Astellas Pharma, Bristol Myers Squibb, Chugai Pharmaceutical, CURED Inc., Daiichi Sankyo, Eisai, FUJIFILM, Kyowa Hakko Kirin, Nippon Shinyaku, Novartis, Otsuka Pharmaceutical, Perseus Proteomics, Pfizer, Sanofi, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Zenyaku Kogyo. Honoraria from Astellas Pharma, Bristol Myers Squibb, and Novartis.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Department and institution in which the work was done: Kyushu University Hospital, Department of Hematology, Oncology & Cardiovascular Medicine. Hamanomachi Hospital, Department of Hematology. Okayama City General Medical Center, Department of Hematology. Osaka Red Cross Hospital, Department of Hematology. Kindai University Hospital, Department of Hematology and Rheumatology. Kansai Medical University Hospital, Department of Hematology-Oncology. Japanese Red Cross Kyoto Daini Hospital, Department of Hematology. Nagoya University Hospital, Department of Hematology. Juntendo University Hospital, Department of Hematology. National Hospital Organization Disaster Medical Center, Department of Hematology. Saitama Medical Center, Saitama Medical University, Department of Hematology. National Hospital Organization Mito Medical Center, Department of Hematology. Sendai Medical Center, Department of Hematology. Aiiku Hospital, Department of Hematology and Blood Disorders Center.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoshida, C., Kondo, T., Ito, T. et al. Real-world treatment patterns and clinical outcomes in patients with AML in Japan who were ineligible for first-line intensive chemotherapy. Int J Hematol 116, 89–101 (2022). https://doi.org/10.1007/s12185-022-03334-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-022-03334-8

Keywords

Search

Navigation