Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells

Ross, David M.; Pagani, Ilaria S.; Shanmuganathan, Naranie; Kok, Chung Hoow; Seymour, John F.; Mills, Anthony K.; Filshie, Robin; Arthur, Christopher; Dang, Phuong; Saunders, Verity A.; Braley, Jodi; Yong, Agnes S. M.; Yeung, David T.; White, Deborah L.; Grigg, Andrew; Schwarer, Anthony P.; Branford, Susan; Hughes, Timothy P.

doi:10.1038/s41375-018-0264-0

Cited by 69 publications

(62 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Eight first‐attempt studies reported late MolRec, with a total of 24/1528 patients (1·6%) between 25 and 52 months (Matsuki et al , ; Rea et al , ; Hernández‐Boluda et al , ; Mahon et al , ; Saussele et al , ; Ross et al , ; Takahashi et al , ). Late MolRec after a second attempt was also reported in 7/92 patients (7·6%) between 25 and 72 months in three studies (Matsuki et al , ; Legros et al , ; Ross et al , ). This underlines the importance of continuing to follow CML patients and that MRFS is not synonymous to ‘cure’.…”

Section: Discussionmentioning

confidence: 79%

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

et al. 2020

View full text Add to dashboard Cite

More than 10 years ago, the first pilot observational study of imatinib discontinuation was reported in chronic myeloid leukaemia (CML) patients in deep molecular response (DMR). Several studies have been published since then, in patients treated with frontline imatinib, or second-generation tyrosine kinase inhibitors (TKI) in first or second line but also on second attempt of TKI discontinuation. Our objective was to estimate, through meta-analyses of the literature data, the probability of molecular recurrence (MolRec) in the time periods of 0-6, 6-12, 12-18 and 18-24 months after a first and second TKI discontinuation and the probability of re-acquisition of DMR after MolRec. The Medline and Scopus databases were searched up to April 2019. The studies were selected by three independent reviewers. Random-effect meta-analyses were conducted using the MetaXL software. The probability of MolRec in the time periods 0-6, 6-12, 12-18 and 18-24 months after the first attempt was respectively 35%, 8%, 3% and 3%, whereas the probability of MolRec in the time periods 0-6, 6-12 and 12-18 after the second attempt was 48%, 27% and 12% respectively. Re-acquisition of a DMR was observed in 90% of patients. Most of the MolRec occur during the first six months in case of a first attempt, whereas the second MolRec occurs over a larger window of time.Keywords: meta-analysis, chronic myeloid leukemia, tyrosine kinase inhibitors discontinuation, first and second attempt. Recently, second attempts to discontinue TKI in patients who relapsed have been reported (Legros et al.

show abstract

Section: Discussionmentioning

confidence: 79%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…208 Other subsequent studies that have evaluated the discontinuation of imatinib have also reported similar findings. [209][210][211][212][213] More recent studies have also confirmed the feasibility of TFR after discontinuation of dasatinib or nilotinib in patients with CP-CML who have achieved and maintained MR4.5 for 12 months after $2 years of TKI therapy in the first-line or second-line setting (TFR rates ranging from 44% to 54%; Table 7). [214][215][216][217][218][219][220] The feasibility of TFR after discontinuation of bosutinib or ponatinib has not yet been evaluated in clinical studies.…”

Section: Discontinuation Of Tki Therapymentioning

confidence: 84%

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Deininger

Shah

Altman³

et al. 2020

Journal of the National Comprehensive Cancer Network

192

210

View full text Add to dashboard Cite

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

show abstract

“…There were no significant differences in patient demographics between patients in the CML8 and CML10 studies (Table1). In the CML8 study, where the MolR criteria were more stringent, 14/22 MolR patients restarted TKI without loss of MMR 24 .…”

Section: Resultsmentioning

confidence: 99%

Successful treatment‐free remission in chronic myeloid leukaemia and its association with reduced immune suppressors and increased natural killer cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

Summary There is currently no biomarker that reliably predicts treatment‐free remission (TFR) in chronic myeloid leukaemia (CML). We characterised effector and suppressor immune responses at the time of tyrosine kinase inhibitor (TKI) cessation in patients from the CML8 and CML10 clinical studies. Natural killer (NK) cells with increased expression of activating NK receptors were higher in patients who achieved TFR. There was no difference in the proportion of CD4+ or CD8+ T cells. Furthermore, we found that FoxP3+ regulatory T cells (T reg) and monocytic myeloid‐derived suppressor cells (Mo‐MDSCs) were concomitantly decreased in TFR patients, suggesting that the effector and suppressor arms of the immune system work in concert to mediate TFR. A discovery cohort (CML10) was used to generate a predictive model, using logistic regression. Patients classified into the high‐risk group were more likely to relapse when compared with the low‐risk group (HR 7·4, 95% CI 2·9‐19·1). The model was successfully validated on the independent CML8 cohort (HR 8·3, 95% CI 2·2–31·3). Effective prediction of TFR success may be obtained with an effector‐suppressor score, calculated using absolute NK cell, T reg, and Mo‐MDSC counts, at TKI cessation, reflecting the contribution of both immune suppressors and effectors in the immunobiology underlying successful TFR.

show abstract

Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells

Cited by 69 publications

References 30 publications

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

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

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Successful treatment‐free remission in chronic myeloid leukaemia and its association with reduced immune suppressors and increased natural killer cells

Contact Info

Product

Resources

About