Undetectable molecular residual disease after omacetaxine and nilotinib combination therapy in an imatinib‐resistant chronic myeloid leukaemia patient harbouring the <i>BCR‐ABL1</i> T315I gatekeeper mutation

Coudé, Marie-Magdelaine; Luycx, Odile; Cariou, Marie-Estelle; Maarek, Odile; Dombret, Hervé; Cayuela, Jean‐Michel; Réa, Delphine

doi:10.1111/j.1365-2141.2011.09016.x

Cited by 13 publications

(9 citation statements)

References 9 publications

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“…Previous studies in a preclinical mouse model and in patients with T315I with prior TKI treatments have shown that omacetaxine treatment reduces the proportion of T315I‐positive cells, and this may enable rechallenge with second‐generation TKIs. Furthermore, 1 patient with CP‐CML who demonstrated pan‐TKI resistance achieved a stable, long‐lasting (>5 years) major molecular response with omacetaxine treatment . Whether this is a direct effect of omacetaxine on the mutated clone or a result of withdrawal of the TKI, as has been previously suggested, cannot be determined in this analysis.…”

Section: Discussionmentioning

confidence: 99%

Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic‐ or accelerated‐phase chronic myeloid leukemia: Results with 24 months of follow‐up

Cortes

Kantarjian

Réa

et al. 2015

Cancer

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Background Omacetaxine, a protein synthesis inhibitor, is indicated in the US for the treatment of patients with chronic (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Methods This final analysis, with 24-month follow-up, includes additional efficacy and safety analyses to assess the benefit of long-term omacetaxine administration (1.25 mg/m2 bid for 14 days q 28 days followed by 7 days q 28 days) in CP- and AP-CML patients receiving >3 cycles. Results Eighteen percent of CP-CML patients achieved major cytogenetic response (MCyR) with a median duration 12.5 months (95% confidence interval [CI], 3.5-not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders and median overall survival (OS) was 40.3 months (95% CI, 23.8-not reached). In patients with AP-CML, 14% achieved or maintained major hematologic response for a median of 4.7 months (95% CI, 3.6-NR); MCyR was not achieved and median OS was 14.3 months (95% CI, 6.7–18.7). In patients with CP- or AP-CML who received >3 cycles of treatment (n=50 and 14, respectively), median OS was 49.3 months (95% CI, 23.8-NR) and 24.6 months (95% CI, 12–37.2), respectively. Grade ≥3 hematologic toxicity was the major side effect (79%/73% in CP-CML/AP-CML), with discontinuation due to toxicity in 10% of CP and 5% of AP patients. Conclusions These results suggest that long-term administration of omacetaxine is feasible with dose adjustments to manage toxicities, and that omacetaxine provides durable benefit in some patients.

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Section: Discussionmentioning

confidence: 99%

Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic‐ or accelerated‐phase chronic myeloid leukemia: Results with 24 months of follow‐up

Cortes

Kantarjian

Réa

et al. 2015

Cancer

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“…Another study reported suppression of CML cells with the T315I mutation and undetectable molecular residual disease in an imatinib-resistant patient treated with omacetaxine and nilotinib combination therapy after single-agent omacetaxine. 160 …”

Section: Available and Future Treatment Approaches To Overcome Resistmentioning

confidence: 99%

Resistance to Tyrosine Kinase Inhibition Therapy for Chronic Myelogenous Leukemia: A Clinical Perspective and Emerging Treatment Options

Jabbour

Cortés

Kantarjian

2013

Clinical Lymphoma Myeloma and Leukemia

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The development of tyrosine kinase inhibitors (TKIs) has led to extended lifespans for many patients with chronic myelogenous leukemia (CML). However, 20% to 30% of patients fail to respond, respond suboptimally, or experience disease relapse after treatment with imatinib. A key factor is drug resistance. The molecular mechanisms implicated in this resistance include those that involve upregulation or mutation of BCR-ABL kinase and those that are BCR-ABL independent. The clinical consequences of these molecular mechanisms of resistance for disease pathogenesis remain open for debate. This review summarizes the molecular mechanisms and clinical consequences of TKI resistance and addresses the current and future treatment approaches for patients with TKI-resistant CML.

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“…Furthermore, there is some evidence that omacetaxine treatment might resensitize the disease to TKIs in some patients, offering the potential for rechallenge with a TKI after omacetaxine therapy. 28,29 …”

Section: Discussionmentioning

confidence: 99%

Subcutaneous Omacetaxine Mepesuccinate in Patients With Chronic-Phase Chronic Myeloid Leukemia Previously Treated With 2 or More Tyrosine Kinase Inhibitors Including Imatinib

Cortes

Nicolini

Wetzler

et al. 2013

Clinical Lymphoma Myeloma and Leukemia

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Undetectable molecular residual disease after omacetaxine and nilotinib combination therapy in an imatinib‐resistant chronic myeloid leukaemia patient harbouring the BCR‐ABL1 T315I gatekeeper mutation

Cited by 13 publications

References 9 publications

Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic‐ or accelerated‐phase chronic myeloid leukemia: Results with 24 months of follow‐up

Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic‐ or accelerated‐phase chronic myeloid leukemia: Results with 24 months of follow‐up

Resistance to Tyrosine Kinase Inhibition Therapy for Chronic Myelogenous Leukemia: A Clinical Perspective and Emerging Treatment Options

Subcutaneous Omacetaxine Mepesuccinate in Patients With Chronic-Phase Chronic Myeloid Leukemia Previously Treated With 2 or More Tyrosine Kinase Inhibitors Including Imatinib

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