Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Hochhaus, Andreas; Saußele, Susanne; Rosti, Gianantonio; Mahon, Franҫois-Xavier; Janssen, Jeroen; Hjorth‐Hansen, Henrik; Richter, Johan; Buske, Christian

doi:10.1093/annonc/mdx219

Cited by 287 publications

(434 citation statements)

References 43 publications

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“…Although this leaves few patients in whom to evaluate the impact of timely monitoring at 18 months, the point estimate for tPCR at 18 months strongly suggests no effect on MMR for timely testing at this time point. Therefore, the results of the current study reiterate the importance of the 3‐month and 12‐month milestones included in the 2013 ELN and the 2017 ESMO guidelines . Monitoring beyond 12 months remains essential but timely monitoring may be less crucial after this time point.…”

Section: Discussionsupporting

confidence: 63%

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Molecular monitoring of therapeutic milestones and clinical outcomes in patients with chronic myeloid leukemia

Klil-Drori

Yin

Azoulay

et al. 2018

Cancer

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Background In the current study, the authors determined whether adhering to molecular monitoring guidelines in patients with chronic myeloid leukemia (CML) is associated with major molecular response (MMR) and assessed barriers to adherent monitoring. Methods Newly treated patients with CML from the Quebec province‐wide CML registry from 2005 to 2016 were included. Timely polymerase chain reaction (tPCR) was defined as the molecular assessment of BCR‐ABL1 at the 3‐month, 12‐month, and 18‐month time points from the initiation of tyrosine kinase inhibitor (TKI) therapy. The cohort was analyzed as a nested case‐control study. Cases with a first‐ever MMR (BCR‐ABL1 ≤0.1%, assessed at any time during follow‐up) were matched to up to 5 controls by duration of TKI therapy, volume of patients with CML at the treatment center, year of cohort entry, and age. Odds ratios (ORs) for the performance of tPCR and MMR were adjusted for sex, comorbidities, type of TKI, and other important covariates. Results The cohort included 496 patients. Of 392 MMR events, 67.9% occurred before 18 months. The performance of tPCR was associated with a doubling of the MMR rate (OR, 2.23; 95% confidence interval [95% CI], 1.56‐3.21) and was similar with 1 to 3 tPCRs performed (P = .67). Furthermore, tPCRs at 3 months (OR, 2.77; 95% CI, 1.81‐4.23) and 12 months (OR, 3.00; 95% CI, 1.64‐5.49) were associated with achieving early MMR, whereas tPCRs at 18 months were not (OR, 1.23; 95% CI, 0.80‐1.89). Low‐volume centers were found to have lower adherence to tPCR (OR, 0.60; 95% CI, 0.40‐0.89). Conclusions Timely molecular assessment at 3 months and 12 months appears to benefit patients with CML. Adherence to timely monitoring should be encouraged, especially in low‐volume treatment centers.

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Section: Discussionsupporting

confidence: 63%

“…The 2013 ELN guidelines changed MMR as the optimal response from 18 months to 12 months . Finally, the 2017 European Society for Medical Oncology (ESMO) guidelines retained the 18‐month time point as a milestone, with less than an MMR considered to be a warning sign just as it is at 12 months …”

Section: Introductionmentioning

confidence: 99%

Molecular monitoring of therapeutic milestones and clinical outcomes in patients with chronic myeloid leukemia

Klil-Drori

Yin

Azoulay

et al. 2018

Cancer

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“…We provisionally recommend at least 5 years of TKI treatment and at least 2 years of MR4.5 confirmed in at least 4 consecutive tests 6 months apart before TKI discontinuation is considered. These recommendations are comparable to those provided in the European Society for Medical Oncology guidelines for CML . Shorter durations of treatment or DMR do not exclude successful TKI discontinuation but are likely to decrease the chances for remaining treatment‐free.…”

Section: Patient Selection For Tki Discontinuationmentioning

confidence: 64%

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: Recommendations for clinical practice from the French Chronic Myeloid Leukemia Study Group

Réa

Amé

Berger

et al. 2018

Cancer

106

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“…Indeed, ESMO recommends at least 5 years of TKI therapy combined with ≥2 years of DMR before TKI discontinuation, while the French CML Study Group requires at least 2 years of MR 4.5 before discontinuation in order to reach the TFR. Moreover, a great uncertainty still remains for the level of MR …”

Section: Discussionmentioning

confidence: 99%

Digital PCR improves the quantitation of DMR and the selection of CML candidates to TKIs discontinuation

et al. 2019

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Treatment‐free remission (TFR) by tyrosine kinase inhibitors (TKI) discontinuation in patients with deep molecular response (DMR) is a paramount goal in the current chronic myeloid leukemia (CML) therapeutic strategy. The best DMR level by real‐time quantitative PCR (RT‐qPCR) for TKI discontinuation is still a matter of debate. To compare the accuracy of digital PCR (dPCR) and RT‐qPCR for BCR‐ABL1 transcript levels detection, 142 CML patients were monitored for a median time of 24 months. Digital PCR detected BCR‐ABL1 transcripts in the RT‐qPCR undetectable cases. The dPCR analysis of the samples, grouped by the MR classes, revealed a significant difference between MR 4.0 and MR 4.5 ( P = 0.0104) or MR 5.0 ( P = 0.0032). The clinical and hematological characteristics of the patients grouped according to DMR classes (MR 4.0 vs MR 4.5‐5.0 ) were superimposable. Conversely, patients with dPCR values <0.468 BCR‐ABL1 copies/µL (as we previously described) showed a longer DMR duration ( P = 0.0220) and mainly belonged to MR 4.5‐5.0 ( P = 0.0442) classes compared to patients with higher dPCR values. Among the 142 patients, 111 (78%) discontinued the TKI treatment; among the 111 patients, 24 (22%) lost the MR 3.0 or MR 4.0 . RT‐qPCR was not able to discriminate patients with higher risk of MR loss after discontinuation ( P = 0.8100). On the contrary, according to dPCR, 12/25 (48%) patients with BCR‐ABL1 values ≥0.468 and 12/86 (14%) patients with BCR‐ABL1 values <0.468 lost DMR in this cohort, respectively ( P = 0.0003). Treatment‐free remission of patients who discontinued TKI with a dPCR <0.468 was significantly higher compared to patients with dPCR ≥ 0.468 (TFR at 2 years 83% vs 52% P = 0.0017, respectively). In conclusion, dPCR resulted in an improved recognition of stable DMR and of candidates to TKI discontinuation.

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Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Cited by 287 publications

References 43 publications

Molecular monitoring of therapeutic milestones and clinical outcomes in patients with chronic myeloid leukemia

Molecular monitoring of therapeutic milestones and clinical outcomes in patients with chronic myeloid leukemia

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: Recommendations for clinical practice from the French Chronic Myeloid Leukemia Study Group

Digital PCR improves the quantitation of DMR and the selection of CML candidates to TKIs discontinuation

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