Tolerability-Adapted Imatinib 800 mg/d Versus 400 mg/d Versus 400 mg/d Plus Interferon-α in Newly Diagnosed Chronic Myeloid Leukemia

Hehlmann, Rüdiger; Lauseker, Michael; Jung-Munkwitz, Susanne; Leitner, Armin; Müller, Martin C.; Pletsch, Nadine; Proetel, Ulrike; Haferlach, Claudia; Schlegelberger, Brigitte; Balleisen, Leopold; Hänel, Mathias; Pfirrmann, Markus; Krause, Stefan W.; Nerl, Christoph; Pralle, H.; Gratwohl, Aloïs; Hossfeld, Dieter K.; Hasford, Joerg; Hochhaus, Andreas; Saußele, Susanne

doi:10.1200/jco.2010.32.0598

Cited by 297 publications

(262 citation statements)

References 38 publications

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“…Notably, although high‐dose imatinib has been associated with poor tolerability (Cortes et al , 2010; Hehlmann et al , 2011), most patients who had nilotinib dose escalation in this study were able to maintain the higher dose, with 83 of 88 remaining on nilotinib 400 mg twice daily at the end of treatment. Although some of these patients (14 of 88; 15·9%) later discontinued treatment due to suboptimal response or treatment failure, the majority (63·6%) achieved MMR by 24 months.…”

Section: Discussionmentioning

confidence: 72%

Nilotinib dose‐optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd

et al. 2017

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SummaryThe Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose‐optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re‐escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2–75·1%) achieved major molecular response (BCR‐ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re‐escalation). The safety profile of nilotinib was consistent with prior studies. The most common non‐haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188).

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Section: Discussionmentioning

confidence: 72%

Nilotinib dose‐optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd

et al. 2017

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“…Assignment to the study arms using imatinib in combination with cytarabine and imatinib after failure of IFN was terminated in 2005. 17 Cytogenetic and molecular analyses Cytogenetic response was determined by conventional metaphase analyses with standard G-banding or fluorescence R-banding techniques after shortterm culture. At least 20 bone marrow cell metaphases were evaluated.…”

Section: Methodsmentioning

confidence: 99%

“…[14][15][16] So far, results of the German CML Study IV showed a superior OS of patients achieving p1% BCR-ABL IS at 12 months of treatment, which was associated with a 3-year survival of 98% as compared with 93% in the 41% group. 17 The aim of the present study was to clarify the relation between early kinetics of molecular and cytogenetic response and the risk for disease progression and death in patients receiving imatinib treatment. Analyzing patients of the German CML Study IV, we report here molecular and cytogenetic milestones to be achieved at 3 and 6 months of treatment to ensure the most favorable outcome and effective TKI treatment.…”

Section: Introductionmentioning

confidence: 99%

Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)

et al. 2012

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“…For patients in CCyR, the achievement and maintenance of a MMR is of debatable significance. Several studies evaluating patients receiving imatinib or second generation have found that patients in CCyR have similar survival whether there is achievement of MMR or not [22,40,41].…”

Section: Important Points For Monitoring and Determining Treatment Famentioning

confidence: 99%

Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

2014

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Disease overview: Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1–2 cases per 100,000 adults, and accounts for ∼15% of newly diagnosed cases of leukemia in adults. Diagnosis: CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR‐ABL fusion oncogene, which in turn translates into a Bcr‐Abl oncoprotein. Frontline therapy: Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib have been approved by the US Food and Drug Administration for the first‐line treatment of patients with newly diagnosed CML in chronic phase (CML‐CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses; their impact on long‐term survival remains to be determined. Salvage therapy: For patients who fail frontline therapy, second‐line options include second and third generation TKIs. Although second and third generation TKIs are potent and specific BCR‐ABL TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as patients comorbidities, disease stage, and BCR‐ABL mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib. Allogeneic transplantation remains an important therapeutic option for CML‐CP who have failed at least 2 TKIs, and for all patients in advanced phase disease. Am. J. Hematol. 89:547–556, 2014. © 2014 Wiley Periodicals, Inc.

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Tolerability-Adapted Imatinib 800 mg/d Versus 400 mg/d Versus 400 mg/d Plus Interferon-α in Newly Diagnosed Chronic Myeloid Leukemia

Abstract: Treatment of early-phase CML with imatinib can be optimized. Early high-dose therapy followed by rapid adaptation to good tolerability increases the rate of MMR at 12 months. Achievement of MMR by month 12 is directly associated with improved survival.

Cited by 297 publications

References 38 publications

Nilotinib dose‐optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd

Nilotinib dose‐optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd

Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)

Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

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