Early switch to second‐line tyrosine kinase inhibitor in chronic myeloid leukemia patients failing to achieve early molecular response

Klil-Drori, Adi J.; Yin, Hui; Azoulay, Laurent; Harnois, Michaël; Gratton, Michel-Olivier; Corpo, Alexa Del; Olney, Harold J.; Delage, Robert; Laneuville, Pierre; Mollica, Luigina; Busque, Lambert; Assouline, Sarit

doi:10.1002/ajh.24838

Cited by 5 publications

(5 citation statements)

References 6 publications

(9 reference statements)

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“…Timely molecular monitoring may result in higher rates of MMR because it may positively influence physician practice, in that suboptimal responses, issues of intolerance or adherence to TKI treatment, or other specific patient factors impacting on response to therapy are addressed in a timely manner. Punctual monitoring allows for the prompt management of suboptimal responses (eg, an early switch to second‐line TKIs after patients fail the 3‐month milestone) …”

Section: Discussionmentioning

confidence: 99%

“…We used data extracted from the Groupe Quebecois de Recherche en Leucemie Myeloide Chronique et Neoplasies Myeloproliferatives (GQR LMC‐NMP) registry . The registry contains demographic, lifestyle, and anthropometric data regarding patients from 20 teaching and nonteaching medical centers across the province of Quebec in Canada, comprising >80% of the provincial points of CML care.…”

Section: Methodsmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

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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“…Furthermore, the apparently higher drug potency displayed by 2G‐TKIs might have been achievable with higher doses of IM . Accordingly, and also considering the better long‐term drug safety profile, IM remains the first line drug of choice in chronic phase CML, regardless of risk score, with early switch to 2G‐TKI recommended for suboptimal response …”

mentioning

confidence: 91%

Revisiting the need for bone marrow examination in chronic myeloid leukemia

2017

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“…Early molecular response (EMR; BCR‐ABL1 ≤10% at 3 months, ≤1% at 6 months) predicts long‐term response and survival . Therefore, EMR achievement at an early time point of treatment has been reported as an important parameter for further treatment and monitoring …”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6] Therefore, EMR achievement at an early time point of treatment has been reported as an important parameter for further treatment and monitoring. [7][8][9] Hughes et al 4 reported that patients achieving EMR at 6 months had superior event-free survival (EFS) and decreased tumor progression. Moreover, numerous studies including those on second-generation (2G) tyrosine kinase inhibitors (TKIs) revealed that patients achieving EMR had significantly lower overall survival (OS), progression-free survival (PFS), complete cytogenetic response (CCyR), major molecular response (MMR), and/or complete molecular response (CMR).…”

Section: Introductionmentioning

confidence: 99%

BCR‐ABL1 transcript levels at 4 weeks have prognostic significance for time‐specific responses and for predicting survival in chronic‐phase chronic myeloid leukemia patients treated with various tyrosine kinase inhibitors

et al. 2018

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The present study aimed to assess the clinical impact of BCR‐ABL1 transcript levels determined at an earlier time point than the 3‐month early molecular response (EMR) in chronic‐phase chronic myeloid leukemia (CML‐CP) patients. BCR‐ABL1 transcript levels of CML‐CP patients (n = 258; median age, 43 [range, 18‐81] years) treated with various tyrosine kinase inhibitors (TKIs) were determined at 4 weeks (28 ± 3 days) and at every 3 months of treatment initiation. At 4 weeks, receiver operating characteristic curves revealed that cutoff values of BCR‐ABL1 transcripts for achieving major molecular responses (MMRs) by 12 and 60 months were 40.89% and 39.16%, respectively (95% CI, 0.658‐0.772 and 95% CI, 0.643‐0.758; P < 0.0001). With 40% of BCR‐ABL1 transcripts at 4 weeks (very early MR; VEMR), patients with VEMR achieved higher 3‐month EMR and 4‐week VEMR significantly associated with higher cumulative incidences of 5‐year MMR (89.1% vs 72.3%; P < 0.001) and 5‐year deep molecular response (DMR) (56.5% vs 29.4%; P = 0.001). Furthermore, event‐free survival (EFS)‐a (93.0% vs 84.8%; P = 0.068) and EFS‐b (71.1% vs 57.9%; P = 0.061) by 5 years were also marginally significant. VEMR and 3‐month EMR were achieved in 89 patients, with significantly superior outcomes. In multivariate analyses, lower leukocyte count (P = 0.008) and frontline second‐generation TKI therapy size (P < 0.001) were significantly associated with VEMR achievement, but not baseline BCR‐ABL1 level and CML duration. In conclusion, the 4‐week BCR‐ABL1 transcript levels including VEMR could be important to predict long‐term outcomes and may provide additional information about innate intrinsic sensitivity to CML among individuals.

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Early switch to second‐line tyrosine kinase inhibitor in chronic myeloid leukemia patients failing to achieve early molecular response

Cited by 5 publications

References 6 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

Revisiting the need for bone marrow examination in chronic myeloid leukemia

BCR‐ABL1 transcript levels at 4 weeks have prognostic significance for time‐specific responses and for predicting survival in chronic‐phase chronic myeloid leukemia patients treated with various tyrosine kinase inhibitors

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