Sustained Complete Cytogenetic Remission in a Patient with Chronic Myeloid Leukemia after Discontinuation of Imatinib Mesylate Therapy

Okabe, Seiichi; Tauchi, Tetsuzo; Ishii, Yuko; Akahane, Daigo; Nunoda, Kousuke; Honda, Seiko; Takaku, Tomoiku; Ohyashiki, Kazuma

doi:10.1532/ijh97.06187

Cited by 7 publications

(3 citation statements)

References 7 publications

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“…Although previous reports showed that the discontinuation of IM in patients with less than an undetectable MR has led to relapse , several studies have reported the possibility of successful IM discontinuation in CML patients with undetectable BCR‐ABL1 transcripts . Mahon et al focused on the patients with undetectable molecular residual disease (UMRD) status of at least 2 years' duration and showed that the probability of persistent UMRD at 12 months after IM cessation was 41%, suggesting that cessation was plausible in some patients with sustained UMRD .…”

Section: Introductionmentioning

confidence: 99%

Predictive factors for successful imatinib cessation in chronic myeloid leukemia patients treated with imatinib

et al. 2013

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Although recent studies have suggested that cessation of imatinib (IM) in chronic myeloid leukemia patients can be associated with sustained response, further validation is needed to explore predictive factors. In a prospective, multicenter study, chronic phase patients were eligible for cessation of IM therapy after more than 3 years if they had no detectable BCR-ABL1 transcript for at least 2 years. A total of 48 patients with a median age of 47 years (19-74 years) were enrolled. Twenty patients received IM for post-transplant relapse. After a median follow-up of 15.8 months (1.4-28.2 months) after IM discontinuation, nine of the non-transplant group lost undetectable molecular residual disease (UMRD) and major molecular response (MMR), whereas none of the 20 patients in the transplant group experienced UMRD loss. Probabilities for sustained MMR and UMRD were 64.4% and 66.3% in the non-transplant group, respectively. Of nine patients re-treated with IM, eight patients re-achieved MMR at a median of 1.7 months (0.9-2.8 months). Seven of these patients re-achieved UMRD at a median of 5.6 months (2.8-12.1 months). Previous transplantation, IM duration, and UMRD duration were significantly associated with sustained molecular responses. Our data strongly suggest that immunological control contributes to sustained suppression of residual leukemia cell expansion and that IM can be safely discontinued in patients with post-transplant relapse. Am. J.

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Section: Introductionmentioning

confidence: 99%

Predictive factors for successful imatinib cessation in chronic myeloid leukemia patients treated with imatinib

et al. 2013

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“…The efficacy and safety of TKI discontinuation strategies and the factors predicting for successful discontinuation have been, and continue to be, investigated in a number of clinical trials. In the wake of numerous case reports (Merante et al, 2005;Breccia et al, 2006;Okabe et al, 2007;Rousselot et al, 2007;Verma et al, 2008;Guastafierro et al, 2009), the STIM (STop IMatinib) clinical trial pioneered the field of imatinib therapy discontinuation in patients achieving stable MR (Mahon et al, 2010). Others have followed (Takahashi et al, 2012;Ross et al, 2013a;Thielen et al, 2013;Rousselot et al, 2014).…”

Section: Mr Milestones Defined In Patients Receiving Tki Therapymentioning

confidence: 99%

Present and future of molecular monitoring in chronic myeloid leukaemia

et al. 2016

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Currently, physicians treating chronic myeloid leukaemia (CML) patients can rely on a wide spectrum of therapeutic options: the best use of such options is essential to achieve excellent clinical outcomes and, possibly, treatment-free remission (TFR). To accomplish this, proper integration of expert clinical and laboratory monitoring of CML patients is fundamental. Molecular response (MR) monitoring of patients at defined time points has emerged as an important success factor for optimal disease management and BCR-ABL1 kinase domain mutation screening is useful to guide therapeutic reassessment in patients who do not achieve optimal responses to tyrosine kinase inhibitor therapy. Deeper MRs might be associated with improved long-term survival outcomes. More importantly, they are considered a gateway to TFR. In molecular biology, novel procedures and technologies are continually being developed. More sophisticated molecular tools and automated analytical solutions are emerging as CML treatment endpoints and expectations become more and more ambitious. Here we provide a critical overview of current and novel methodologies, present their strengths and pitfalls and discuss what their present and future role might be.

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“…One of them is the concept of treatment free remission (TFR), arguing the necessity of life long TKI. Stopping TKI treatment was reported previously (4)(5)(6)(7)(8)(9)(10)(11)(12), but it was not landscape changing until the landmark stop TKI trials from French (13) and Australia (14) reported about 40% of CML patients, who had achieved complete molecular response (CMR), i.e. undetectable BCR-ABL1 gene from qPCR, for at least two years, were able to stop TKI safely and remain in TFR.…”

Section: Introductionmentioning

confidence: 99%

A randomized controlled trial comparing peginterferon-α-2a versus observation after stopping tyrosine kinase inhibitor in chronic myeloid leukemia patients with deep molecular response for at least two years

Kuan

Chang

Phan

et al. 2020

Preprint

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BackgroundInterferon (IFN) is a logical possibility to increase treatment free remission (TFR) rate in chronic myeloid leukemia (CML). We conducted the first randomized controlled trial comparing the use of pegIFN versus observation in CML patients attempting TFR.MethodsAdult CML patients with stable deep molecular response for ≥ 2 years with ≥ 2 readings of MR4.5 were randomized into two arms -- subcutaneous pegIFN-α-2a starting at 180 µg weekly for a year, followed by observation, or observation.ResultsA total of 30 patients were recruited (pegIFN n = 15, observation n = 15). Median follow-up was 38.1 months (range 15.9–49.4) and 23.8 (1.5–51.0) in pegIFN and observation arm, respectively. A total of 11 patients relapsed (pegIFN n = 4, observation n = 7). The median time of relapse was 13.1 months (range 9.2 to 25.5) and 4.4 (1.2 to 13.6) in pegIFN and observation arm, respectively. Only 8 out of 15 (53%) patients completed 52 doses of pegIFN with mean dose of 43 out of 52 doses (range 20 to 52). Dose of tolerable pegIFN was age dependent.ConclusionPegIFN is a potential consolidative therapy to increase TFR.Trial registration:(1) Malaysia National Medical Research Register (NMRR): NMRR-13-1186-15491. Approved 23rd September 2014, https://www.nmrr.gov.my/fwbLoginPage.jsp(2) ClinicalTrials.gov: NCT02381379. Registered on 24th Feb 2015, https://clinicaltrials.gov/ct2/results?cond=&term=NCT02381379&cntry=&state=&city=&dist=

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Sustained Complete Cytogenetic Remission in a Patient with Chronic Myeloid Leukemia after Discontinuation of Imatinib Mesylate Therapy

Cited by 7 publications

References 7 publications

Predictive factors for successful imatinib cessation in chronic myeloid leukemia patients treated with imatinib

Predictive factors for successful imatinib cessation in chronic myeloid leukemia patients treated with imatinib

Present and future of molecular monitoring in chronic myeloid leukaemia

A randomized controlled trial comparing peginterferon-α-2a versus observation after stopping tyrosine kinase inhibitor in chronic myeloid leukemia patients with deep molecular response for at least two years

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