Skip to main content
Top

Open Access 10-01-2025 | Chronic Myeloid Leukemia | Case Report

Sustained treatment-free remission in two chronic myeloid leukemia patients after asciminib discontinuation: a report of two cases

Authors: Arjen Yousefi, Mark-David Levin, Jan J. Cornelissen, Peter E. Westerweel

Published in: Annals of Hematology

Login to get access

Abstract

Selected chronic myeloid leukemia (CML) patients may discontinue their tyrosine kinase inihibitor (TKI) in an attempt to achieve sustained treatment-free remission (TFR), which mitigates therapy-related side effects and limits treatment costs. TFR has been extensively studied following the discontinuation of adenosine triphosphate (ATP) – competitive TKI. However, there is minimal data concerning TFR after the discontinuation of the novel TKI asciminib. Here, we present two CML patients intolerant to multiple ATP-competitive TKIs who achieved a deep molecular response (DMR) during asciminib treatment and sustained this remission after asciminib discontinuation. One of the cases developed transient myalgia and arthralgia after asciminib discontinuation consistent with a TKI withdrawal syndrome. Both patients have been free of molecular relapse for more than at least 8 months after TKI discontinuation without increase in molecular BCR::ABL1 signal. These two cases provide proof of principle that sustained TFR after discontinuing asciminib in CML patients is feasible.
Literature
1.
go back to reference Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, Clark RE, Cortes JE, Deininger MW, Guilhot F, Hjorth-Hansen H, Hughes TP, Janssen JJWM, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Mayer J, Nicolini F, Niederwieser D, Pane F, Radich JP, Rea D, Richter J, Rosti G, Rousselot P, Saglio G, Saußele S, Soverini S, Steegmann JL, Turkina A, Zaritskey A, Hehlmann R (2020) European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 34(4):966–984. https://doi.org/10.1038/s41375-020-0776-2CrossRefPubMedPubMedCentral Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, Clark RE, Cortes JE, Deininger MW, Guilhot F, Hjorth-Hansen H, Hughes TP, Janssen JJWM, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Mayer J, Nicolini F, Niederwieser D, Pane F, Radich JP, Rea D, Richter J, Rosti G, Rousselot P, Saglio G, Saußele S, Soverini S, Steegmann JL, Turkina A, Zaritskey A, Hehlmann R (2020) European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 34(4):966–984. https://​doi.​org/​10.​1038/​s41375-020-0776-2CrossRefPubMedPubMedCentral
2.
go back to reference Dulucq S, Astrugue C, Etienne G, Mahon FX, Benard A (2020) Risk of molecular recurrence after tyrosine kinase inhibitor discontinuation in chronic myeloid leukaemia patients: a systematic review of literature with a meta-analysis of studies over the last ten years. Br J Haematol 189(3):452–468. https://doi.org/10.1111/bjh.16408CrossRefPubMed Dulucq S, Astrugue C, Etienne G, Mahon FX, Benard A (2020) Risk of molecular recurrence after tyrosine kinase inhibitor discontinuation in chronic myeloid leukaemia patients: a systematic review of literature with a meta-analysis of studies over the last ten years. Br J Haematol 189(3):452–468. https://​doi.​org/​10.​1111/​bjh.​16408CrossRefPubMed
3.
go back to reference Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, Marzinzik AL, Pelle X, Donovan J, Zhu W, Buonamici S, Hassan AQ, Lombardo F, Iyer V, Palmer M, Berellini G, Dodd S, Thohan S, Bitter H, Branford S, Ross DM, Hughes TP, Petruzzelli L, Vanasse KG, Warmuth M, Hofmann F, Keen NJ, Sellers WR (2017) The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature 543(7647):733–737. https://doi.org/10.1038/nature21702CrossRefPubMed Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, Marzinzik AL, Pelle X, Donovan J, Zhu W, Buonamici S, Hassan AQ, Lombardo F, Iyer V, Palmer M, Berellini G, Dodd S, Thohan S, Bitter H, Branford S, Ross DM, Hughes TP, Petruzzelli L, Vanasse KG, Warmuth M, Hofmann F, Keen NJ, Sellers WR (2017) The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature 543(7647):733–737. https://​doi.​org/​10.​1038/​nature21702CrossRefPubMed
4.
go back to reference Hochhaus A, Réa D, Boquimpani C, Minami Y, Cortes JE, Hughes TP, Apperley JF, Lomaia E, Voloshin S, Turkina A, Kim DW, Abdo A, Fogliatto LM, le Coutre P, Sasaki K, Kim DDH, Saussele S, Annunziata M, Chaudhri N, Chee L, García-Gutiérrez V, Kapoor S, Allepuz A, Quenet S, Bédoucha V, Mauro MJ (2023) Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Leukemia 37(3):617–626. https://doi.org/10.1038/s41375-023-01829-9CrossRefPubMedPubMedCentral Hochhaus A, Réa D, Boquimpani C, Minami Y, Cortes JE, Hughes TP, Apperley JF, Lomaia E, Voloshin S, Turkina A, Kim DW, Abdo A, Fogliatto LM, le Coutre P, Sasaki K, Kim DDH, Saussele S, Annunziata M, Chaudhri N, Chee L, García-Gutiérrez V, Kapoor S, Allepuz A, Quenet S, Bédoucha V, Mauro MJ (2023) Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Leukemia 37(3):617–626. https://​doi.​org/​10.​1038/​s41375-023-01829-9CrossRefPubMedPubMedCentral
9.
go back to reference Okada M, Imagawa J, Tanaka H, Nakamae H, Hino M, Murai K, Ishida Y, Kumagai T, Sato S, Ohashi K, Sakamaki H, Wakita H, Uoshima N, Nakagawa Y, Minami Y, Ogasawara M, Takeoka T, Akasaka H, Utsumi T, Uike N, Sato T, Ando S, Usuki K, Mizuta S, Hashino S, Nomura T, Shikami M, Fukutani H, Ohe Y, Kosugi H, Shibayama H, Maeda Y, Fukushima T, Yamazaki H, Tsubaki K, Kukita T, Adachi Y, Nataduka T, Sakoda H, Yokoyama H, Okamoto T, Shirasugi Y, Onishi Y, Nohgawa M, Yoshihara S, Morita S, Sakamoto J, Kimura S, DADI Trial Group, Japan (2018) Final 3-year results of the Dasatinib Discontinuation Trial in patients with chronic myeloid leukemia who received Dasatinib as a second-line treatment. Clin Lymphoma Myeloma Leuk 18(5):353–360e1. https://doi.org/10.1016/j.clml.2018.03.004CrossRefPubMed Okada M, Imagawa J, Tanaka H, Nakamae H, Hino M, Murai K, Ishida Y, Kumagai T, Sato S, Ohashi K, Sakamaki H, Wakita H, Uoshima N, Nakagawa Y, Minami Y, Ogasawara M, Takeoka T, Akasaka H, Utsumi T, Uike N, Sato T, Ando S, Usuki K, Mizuta S, Hashino S, Nomura T, Shikami M, Fukutani H, Ohe Y, Kosugi H, Shibayama H, Maeda Y, Fukushima T, Yamazaki H, Tsubaki K, Kukita T, Adachi Y, Nataduka T, Sakoda H, Yokoyama H, Okamoto T, Shirasugi Y, Onishi Y, Nohgawa M, Yoshihara S, Morita S, Sakamoto J, Kimura S, DADI Trial Group, Japan (2018) Final 3-year results of the Dasatinib Discontinuation Trial in patients with chronic myeloid leukemia who received Dasatinib as a second-line treatment. Clin Lymphoma Myeloma Leuk 18(5):353–360e1. https://​doi.​org/​10.​1016/​j.​clml.​2018.​03.​004CrossRefPubMed
10.
go back to reference Rea D, Nicolini FE, Tulliez M, Guilhot F, Guilhot J, Guerci-Bresler A, Gardembas M, Coiteux V, Guillerm G, Legros L, Etienne G, Pignon JM, Villemagne B, Escoffre-Barbe M, Ianotto JC, Charbonnier A, Johnson-Ansah H, Noel MP, Rousselot P, Mahon FX (2017) Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood 129(7):846–854 France Intergroupe des Leucémies Myéloïdes Chroniques. https://doi.org/10.1182/blood-2016-09-742205CrossRefPubMed Rea D, Nicolini FE, Tulliez M, Guilhot F, Guilhot J, Guerci-Bresler A, Gardembas M, Coiteux V, Guillerm G, Legros L, Etienne G, Pignon JM, Villemagne B, Escoffre-Barbe M, Ianotto JC, Charbonnier A, Johnson-Ansah H, Noel MP, Rousselot P, Mahon FX (2017) Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood 129(7):846–854 France Intergroupe des Leucémies Myéloïdes Chroniques. https://​doi.​org/​10.​1182/​blood-2016-09-742205CrossRefPubMed
11.
go back to reference Richter J, Söderlund S, Lübking A, Dreimane A, Lotfi K, Markevärn B, Själander A, Saussele S, Olsson-Strömberg U, Stenke L (2014) Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome? J Clin Oncol 32(25):2821–2823. https://doi.org/10.1200/JCO.2014.55.6910CrossRefPubMed Richter J, Söderlund S, Lübking A, Dreimane A, Lotfi K, Markevärn B, Själander A, Saussele S, Olsson-Strömberg U, Stenke L (2014) Musculoskeletal pain in patients with chronic myeloid leukemia after discontinuation of imatinib: a tyrosine kinase inhibitor withdrawal syndrome? J Clin Oncol 32(25):2821–2823. https://​doi.​org/​10.​1200/​JCO.​2014.​55.​6910CrossRefPubMed
12.
go back to reference Lee SE, Choi SY, Song HY, Kim SH, Choi MY, Park JS, Kim HJ, Kim SH, Zang DY, Oh S, Kim H, Do YR, Kwak JY, Kim JA, Kim DY, Mun YC, Lee WS, Chang MH, Park J, Kwon JH, Kim DW (2016) Imatinib Withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica 101(6):717–723. https://doi.org/10.3324/haematol.2015.139899CrossRefPubMedPubMedCentral Lee SE, Choi SY, Song HY, Kim SH, Choi MY, Park JS, Kim HJ, Kim SH, Zang DY, Oh S, Kim H, Do YR, Kwak JY, Kim JA, Kim DY, Mun YC, Lee WS, Chang MH, Park J, Kwon JH, Kim DW (2016) Imatinib Withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica 101(6):717–723. https://​doi.​org/​10.​3324/​haematol.​2015.​139899CrossRefPubMedPubMedCentral
Metadata
Title
Sustained treatment-free remission in two chronic myeloid leukemia patients after asciminib discontinuation: a report of two cases
Authors
Arjen Yousefi
Mark-David Levin
Jan J. Cornelissen
Peter E. Westerweel
Publication date
10-01-2025
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-024-06170-4

ASH 2024 Annual Meeting Coverage

inMIND supports tafasitamab addition in follicular lymphoma

Combining tafasitamab with lenalidomide and rituximab significantly improves progression-free survival for patients with relapsed or refractory follicular lymphoma.

Featuring the official presentation video

Read more
SPONSORED

Recent advances in the use of CAR T-cell therapies in relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma

In this webinar, Professor Martin Dreyling and an esteemed international panel of CAR T-cell therapy experts discuss the latest data on the safety, efficacy, and clinical impact of CAR T-cell therapies in the treatment of r/r DLBCL and r/r FL.

Please note, this webinar is not intended for healthcare professionals based in the US and UK.

Sponsored by:
  • Novartis Pharma AG
Chaired by: Prof. Martin Dreyling
Developed by: Springer Healthcare
Watch now