Phase 2 study of nilotinib in pediatric patients with Philadelphia chromosome–positive chronic myeloid leukemia

Hijiya, Nobuko; Maschan, Alexey; Rizzari, Carmelo; Shimada, Hideaki; Dufour, Carlo; Goto, Hiroaki; Kang, Hyoung Jin; Guinipero, Terri; Karakaş, Zeynep; Bautista, Francisco; Ducassou, Stéphane; Yoo, Keon Hee; Zwaan, C. Michel; Millot, Frédéric; Aimone, Paola; Allepuz, Alejandro; Quenet, Sara; Hourcade‐Potelleret, Florence; Hertle, Sabine; Sosothikul, Darintr

doi:10.1182/blood.2019000069

Cited by 42 publications

(70 citation statements)

References 29 publications

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“…However, there was no increased rate of grade 3 AEs in patients treated with multiagent chemotherapy. Overall, rates of serious AEs were lower in this study than reported in adults, which is consistent with studies of second‐generation TKIs in paediatrics (Hijiya et al , ; Gore et al , ).…”

Section: Patient and Disease Characteristics Treatment Details Toxisupporting

confidence: 91%

Experience with ponatinib in paediatric patients with leukaemia

et al. 2020

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Ponatinib has proven to be effective in adults with Philadelphia chromosome-positive leukaemias, but data in paediatrics are scarce. Among paediatric patients with chronic myeloid leukaemia (n = 9) or acute lymphoblastic leukaemia (n = 12) treated with varying doses of ponatinib in 13 centres, 71% showed a decrease in disease burden after a median of three months. Ponatinib was well tolerated, with grade 3 toxicities occurring in 29% of patients. Toxicities were similar to those reported in adults, with the exception of arterial thrombotic events, which were not observed. Ponatinib has a favourable safety profile in this paediatric cohort, but dose-finding studies are needed.

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Section: Patient and Disease Characteristics Treatment Details Toxisupporting

confidence: 91%

Experience with ponatinib in paediatric patients with leukaemia

et al. 2020

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“…[14][15][16] The second-generation TKIs (2G-TKIs) dasatinib and nilotinib were approved recently as first-line treatment in children, which has expanded treatment options and made allogeneic stem cell transplantation (allo-SCT) a third-line treatment. 17,18 However, because children are actively growing during TKI treatment, they face unique side effects not seen in adults, such as growth disturbance. [19][20][21][22][23] Discontinuing TKIs in patients with a deep and sustained molecular response is feasible in adult patients.…”

Section: Introductionmentioning

confidence: 99%

How I treat chronic myeloid leukemia in children and adolescents

Hijiya

Suttorp

2019

Blood

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112

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Evidence-based recommendations have been established for treatment of chronic myeloid leukemia (CML) in adults treated with tyrosine kinase inhibitors (TKIs), but the rarity of this leukemia in children and adolescents makes it challenging to develop similar recommendations in pediatrics. In addition to imatinib, which was approved for pediatric CML in 2003, the second-generation TKIs dasatinib and nilotinib were recently approved for use in children, expanding the therapeutic options and pushing allogeneic stem cell transplantation to a third-line treatment of most pediatric cases. Yet, without sufficient data on efficacy and safety specific to pediatric patients, the selection of a TKI continues to rely on clinical experience in adults. Here, we present 4 case scenarios highlighting common yet challenging issues encountered in the treatment of pediatric CML (suboptimal response, poor treatment adherence, growth retardation, and presentation in advanced phases). Limited experience with very young children, the transition of teenagers to adult medicine, and the goal of achieving treatment-free remission for this rare leukemia are additional significant obstacles that require further clinical investigation through international collaboration.

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“…[5][6][7] More recently, initial pediatric data are now available for second-generation tyrosine kinase inhibitors (TKIs), including dasatinib and nilotinib. 8,9 TKI monotherapy is considered standard therapy for those presenting in CP with adequate disease response. HSCT is now considered only in a subset of children with CML, namely those who present with, or progress to, blast phase.…”

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confidence: 99%

Outcomes of children with chronic myeloid leukemia: A population‐based cohort study

Egan

Athale

Johnston

et al. 2020

Pediatric Blood & Cancer

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Objective Chronic myeloid leukemia (CML) is a rare disease in childhood. While hematopoietic stem cell transplant (HSCT) was the treatment of choice for CML prior to 2000, the introduction of tyrosine kinase inhibitors (TKIs) changed the management of this disease. This population‐based analysis was conducted in the province of Ontario, Canada to gather information on treatment choices and outcomes of childhood CML. Method Using a provincial childhood cancer registry and retrospective review of patient medical records for patients < 18 years diagnosed with CML between 1985 and 2018, data on presenting features, treatment, and outcomes were collected from 52 patients. Results Patients treated before the introduction of TKIs (before 2002) mainly received HSCT and had an overall survival (OS) of 64% at a median follow up of 6 years. The OS of all patients treated in the TKI era (2002 and after) was 90% at a median follow up of 3 years. All three deaths in the TKI era were related to HSCT complications. Survival of patients who remained on a TKI was significantly improved compared to those who underwent HSCT post‐TKI therapy (100% vs 66%, P = .008). TKIs were well tolerated. Conclusion Given the increased mortality associated with HSCT in our cohort, further advances in HSCT may be required to outweigh the benefits of a TKI monotherapy approach in the majority of childhood CML patients. We believe HSCT should be considered in only a limited subset of pediatric patients with CML.

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Phase 2 study of nilotinib in pediatric patients with Philadelphia chromosome–positive chronic myeloid leukemia

Abstract: Key Points Nilotinib demonstrated efficacy and a manageable safety profile in pediatric patients with newly diagnosed and pretreated Ph+ CML-CP.

Cited by 42 publications

References 29 publications

Experience with ponatinib in paediatric patients with leukaemia

Experience with ponatinib in paediatric patients with leukaemia

How I treat chronic myeloid leukemia in children and adolescents

Outcomes of children with chronic myeloid leukemia: A population‐based cohort study

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