Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Discontinuation of Imatinib: A Tyrosine Kinase Inhibitor Withdrawal Syndrome?

Richter, Johan; Söderlund, Stina; Lübking, Anna; Dreimane, Arta; Lotfi, Kourosh; Markevärn, Berit; Själander, Anders; Saußele, Susanne; Olsson‐Strömberg, Ulla; Stenke, Leif

doi:10.1200/jco.2014.55.6910

Cited by 123 publications

(121 citation statements)

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“…Preliminary results regarding the analysis of the quality of life showed also a trend toward increased pain scores between screening and months 1 and 3 (21.2% of patients at each time point reported new or worsening pain), a "withdrawal syndrome" previously reported in other trials [26]; the investigation of this phenomenon will require further studies. Within this analysis, a significant decrease in "fatigue" emerged after 1 month from imatinib discontinuation (P50.0004).…”

Section: Discussionmentioning

confidence: 74%

Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

et al. 2015

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Imatinib is effective for the treatment of chronic myeloid leukemia (CML). However even undetectable BCR-ABL1 by Q-RT-PCR does not equate to eradication of the disease. Digital-PCR (dPCR), able to detect 1 BCR-ABL1 positive cell out of 10 7 , has been recently developed. The ISAV study is a multicentre trial aimed at validating dPCR to predict relapses after imatinib discontinuation in CML patients with undetectable Q-RT-PCR. CML patients under imatinib therapy since more than 2 years and with undetectable PCR for at least 18 months were eligible. Patients were monitored by standard Q-RT-PCR for 36 months. Patients losing molecular remission (two consecutive positive Q-RT-PCR with at least 1 BCR-ABL1/ABL1 value above 0.1%) resumed imatinib. The study enrolled 112 patients, with a median follow-up of 21.6 months. Fifty-two of the 108 evaluable patients (48.1%), relapsed; 73.1% relapsed in the first 9 months but 14 late relapses were observed between 10 and 22 months. Among the 56 not-relapsed patients, 40 (37.0% of total) regained Q-RT-PCR positivity but never lost MMR. dPCR results showed a significant negative predictive value ratio of 1.115 [95% CI: 1.013-1.227]. An inverse relationship between patients age and risk of relapse was evident: 95% of patients <45 years relapsed versus 42% in the class 45 to <65 years and 33% of patients 65 years [P(v 2 ) < 0.0001]. Relapse rates ranged between 100% (<45 years, dPCR1) and 36% (>45 years, dPCR-). Imatinib can be safely discontinued in the setting of continued PCR negativity; age and dPCR results can predict relapse.

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Section: Discussionmentioning

confidence: 74%

Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

et al. 2015

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“…Secondly, this practice-changing view is reinforced by the demonstration of general improvement of adverse events in both the MMR and MR4 cohorts, with only mild (none > grade 2 severity) and transient evidence of the musculoskeletal symptoms that have recently been described on complete TKI withdrawal 9,15 . Although these and other symptoms generally improved during de-escalation as shown in Figure 3, this trend was not of sufficient strength to be detectable by the quality of life assessment tools used here, emphasising their inappropriateness for well controlled CML patients in the TKI era 16,17 .…”

Section: Discussionmentioning

confidence: 99%

De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial

Clark

Polydoros

Apperley

et al. 2017

The Lancet Haematology

106

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Clark, R. E. et al. (2017) De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial. Lancet Haematology, 4(7), e310-e316. (doi:10.1016/S2352-3026(17)30066-2) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.

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“…In these studies, patients experienced many potential positive impacts of TFR, and relief of TKI-related AEs were the most frequently reported, although discontinuation of TKIs could be associated with a toxicity, so-called 'withdrawal syndrome,' presenting with musculoskeletal pain which starts, or worsens after 1-6 weeks from TKI discontinuation [16]. In these trials, approximately 50-60% of the patients were molecular relapse free; however, the clinical data regarding the TKI discontinuation are still growing, and studies on large series should be planned in order to accumulate more mature data [17].…”

Section: Treatment-free Remission (Tfr) In Patients With CMLmentioning

confidence: 99%

Tyrosine kinase inhibitor (TKI) therapy for newly-diagnosed patients with chronic myeloid leukemia: focusing on TKI discontinuation due to adverse events – is better always good?

Eşkazan

Özmen

2017

Expert Review of Hematology

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Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Discontinuation of Imatinib: A Tyrosine Kinase Inhibitor Withdrawal Syndrome?

Cited by 123 publications

References 4 publications

Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial

Tyrosine kinase inhibitor (TKI) therapy for newly-diagnosed patients with chronic myeloid leukemia: focusing on TKI discontinuation due to adverse events – is better always good?

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