The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study

Nobuko Hijiya; Alexey Maschan; Carmelo Rizzari; Hiroyuki Shimada; Carlo Dufour; Hiroaki Goto; Hyoung Jin Kang; Terri Guinipero; Zeynep Karakas; Francisco Bautista; Stéphane Ducassou; Keon Hee Yoo; Christian Michel Zwaan; Frédéric Millot; Briana C. Patterson; Jill Samis; Miguel Izquierdo; Ksenia Titorenko; Sai Li; Darintr Sosothikul

doi:10.1182/bloodadvances.2023010122

The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study

Nobuko Hijiya^*
, Alexey Maschan
, Carmelo Rizzari
, Hiroyuki Shimada
, Carlo Dufour
, Hiroaki Goto
, Hyoung Jin Kang
, Terri Guinipero
, Zeynep Karakas
, Francisco Bautista
, Stéphane Ducassou
, Keon Hee Yoo
, Christian Michel Zwaan
, Frédéric Millot
, Briana C. Patterson
, Jill Samis
, Miguel Izquierdo
, Ksenia Titorenko
, Sai Li
, Darintr Sosothikul

^*Corresponding author for this work

Pediatrics

Columbia University
Dmitriy Rogachev Federal Center for Pediatric Hematology
University of Milan - Bicocca
Keio University School of Medicine
IRCCS Istituto Giannina Gaslini - Genova
Kanagawa Children's Medical Center
Seoul National University College of Medicine
Seoul National University Cancer Research Institute
Seoul National University Children’s Hospital
Wide River Institute of Immunology
Ohio State University
Istanbul University
Hospital Infantil Universitario Nino Jesus de Madrid
Princess Máxima Center for Pediatric Oncology
Groupe hospitalier Pellegrin
Sungkyunkwan University
CHU de Poitiers
Emory University School of Medicine
Children's Memorial Hospital
Novartis
Novartis Pharmaceuticals Corporations (Germany)
Chulalongkorn University

Research output: Contribution to journal › Article › Academic › peer-review

8 Citations (Scopus)

21 Downloads (Pure)

Abstract

The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/ intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome–positive (Ph⁺) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m² twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.5 and 51.9 months, respectively). In the R/I cohort, the cumulative major molecular response (MMR; BCR::ABL1 international scale [IS] ≤ 0.1%) rate was 60.6%, and no patients had a confirmed loss of MMR. Among ND patients, the best overall MMR rate was 76.0%; 3 patients had a confirmed loss of MMR. The cumulative molecular response MR⁴ (BCR::ABL1^IS ≤ 0.01%) and MR^4.5 (BCR::ABL1^IS ≤ 0.0032%) rates by 66 cycles were 27.3% and 12.1% in the R/I cohort, and 56.0% and 44.0% in the ND cohort, respectively. The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to ~5 years) data support the efficacy and safety of nilotinib in pediatric patients with Ph⁺ CML-CP. This trial was registered at www.clinicaltrials.gov.uk as #NCT01844765.

Original language	English
Pages (from-to)	7279-7289
Number of pages	11
Journal	Blood Advances
Volume	7
Issue number	23
DOIs	https://doi.org/10.1182/bloodadvances.2023010122
Publication status	Published - 1 Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 by The American Society of Hematology.

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The long-term efficacy and safety of nilotinib in pediatric patients with CMLFinal published version, 1.08 MBLicence: CC BY-NC-ND

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Hijiya, N., Maschan, A., Rizzari, C., Shimada, H., Dufour, C., Goto, H., Kang, H. J., Guinipero, T., Karakas, Z., Bautista, F., Ducassou, S., Yoo, K. H., Zwaan, C. M., Millot, F., Patterson, B. C., Samis, J., Izquierdo, M., Titorenko, K., Li, S., & Sosothikul, D. (2023). The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study. Blood Advances, 7(23), 7279-7289. https://doi.org/10.1182/bloodadvances.2023010122

@article{436de48c29e14e39a827fc1130466e5f,

title = "The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study",

abstract = "The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/ intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m2 twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.5 and 51.9 months, respectively). In the R/I cohort, the cumulative major molecular response (MMR; BCR::ABL1 international scale [IS] ≤ 0.1\%) rate was 60.6\%, and no patients had a confirmed loss of MMR. Among ND patients, the best overall MMR rate was 76.0\%; 3 patients had a confirmed loss of MMR. The cumulative molecular response MR4 (BCR::ABL1IS ≤ 0.01\%) and MR4.5 (BCR::ABL1IS ≤ 0.0032\%) rates by 66 cycles were 27.3\% and 12.1\% in the R/I cohort, and 56.0\% and 44.0\% in the ND cohort, respectively. The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to \textasciitilde{}5 years) data support the efficacy and safety of nilotinib in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov.uk as \#NCT01844765.",

author = "Nobuko Hijiya and Alexey Maschan and Carmelo Rizzari and Hiroyuki Shimada and Carlo Dufour and Hiroaki Goto and Kang, \{Hyoung Jin\} and Terri Guinipero and Zeynep Karakas and Francisco Bautista and St{\'e}phane Ducassou and Yoo, \{Keon Hee\} and Zwaan, \{Christian Michel\} and Fr{\'e}d{\'e}ric Millot and Patterson, \{Briana C.\} and Jill Samis and Miguel Izquierdo and Ksenia Titorenko and Sai Li and Darintr Sosothikul",

note = "Publisher Copyright: {\textcopyright} 2023 by The American Society of Hematology.",

year = "2023",

month = dec,

day = "1",

doi = "10.1182/bloodadvances.2023010122",

language = "English",

volume = "7",

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Hijiya, N, Maschan, A, Rizzari, C, Shimada, H, Dufour, C, Goto, H, Kang, HJ, Guinipero, T, Karakas, Z, Bautista, F, Ducassou, S, Yoo, KH, Zwaan, CM, Millot, F, Patterson, BC, Samis, J, Izquierdo, M, Titorenko, K, Li, S & Sosothikul, D 2023, 'The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study', Blood Advances, vol. 7, no. 23, pp. 7279-7289. https://doi.org/10.1182/bloodadvances.2023010122

TY - JOUR

T1 - The long-term efficacy and safety of nilotinib in pediatric patients with CML

T2 - a 5-year update of the DIALOG study

AU - Hijiya, Nobuko

AU - Maschan, Alexey

AU - Rizzari, Carmelo

AU - Shimada, Hiroyuki

AU - Dufour, Carlo

AU - Goto, Hiroaki

AU - Kang, Hyoung Jin

AU - Guinipero, Terri

AU - Karakas, Zeynep

AU - Bautista, Francisco

AU - Ducassou, Stéphane

AU - Yoo, Keon Hee

AU - Zwaan, Christian Michel

AU - Millot, Frédéric

AU - Patterson, Briana C.

AU - Samis, Jill

AU - Izquierdo, Miguel

AU - Titorenko, Ksenia

AU - Li, Sai

AU - Sosothikul, Darintr

PY - 2023/12/1

Y1 - 2023/12/1

N2 - The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/ intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m2 twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.5 and 51.9 months, respectively). In the R/I cohort, the cumulative major molecular response (MMR; BCR::ABL1 international scale [IS] ≤ 0.1%) rate was 60.6%, and no patients had a confirmed loss of MMR. Among ND patients, the best overall MMR rate was 76.0%; 3 patients had a confirmed loss of MMR. The cumulative molecular response MR4 (BCR::ABL1IS ≤ 0.01%) and MR4.5 (BCR::ABL1IS ≤ 0.0032%) rates by 66 cycles were 27.3% and 12.1% in the R/I cohort, and 56.0% and 44.0% in the ND cohort, respectively. The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to ~5 years) data support the efficacy and safety of nilotinib in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov.uk as #NCT01844765.

AB - The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/ intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m2 twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.5 and 51.9 months, respectively). In the R/I cohort, the cumulative major molecular response (MMR; BCR::ABL1 international scale [IS] ≤ 0.1%) rate was 60.6%, and no patients had a confirmed loss of MMR. Among ND patients, the best overall MMR rate was 76.0%; 3 patients had a confirmed loss of MMR. The cumulative molecular response MR4 (BCR::ABL1IS ≤ 0.01%) and MR4.5 (BCR::ABL1IS ≤ 0.0032%) rates by 66 cycles were 27.3% and 12.1% in the R/I cohort, and 56.0% and 44.0% in the ND cohort, respectively. The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to ~5 years) data support the efficacy and safety of nilotinib in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov.uk as #NCT01844765.

UR - https://www.scopus.com/pages/publications/85179609439

U2 - 10.1182/bloodadvances.2023010122

DO - 10.1182/bloodadvances.2023010122

M3 - Article

C2 - 37738125

AN - SCOPUS:85179609439

SN - 2473-9529

VL - 7

SP - 7279

EP - 7289

JO - Blood Advances

JF - Blood Advances

IS - 23

ER -

The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study

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