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

Author:

Hijiya Nobuko1ORCID,Maschan Alexey2ORCID,Rizzari Carmelo3ORCID,Shimada Hiroyuki4ORCID,Dufour Carlo5,Goto Hiroaki6,Kang Hyoung Jin78910,Guinipero Terri11,Karakas Zeynep12,Bautista Francisco1314ORCID,Ducassou Stéphane15,Yoo Keon Hee16,Zwaan Christian Michel1417,Millot Frédéric18,Patterson Briana C.19,Samis Jill20ORCID,Izquierdo Miguel21,Titorenko Ksenia22ORCID,Li Sai21,Sosothikul Darintr23ORCID

Affiliation:

1. 1Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Irving Medical Center, New York, NY

2. 2Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia

3. 3Pediatria, Fondazione IRCSS San Gerardo dei Tintori, Universitá di Milano-Bicocca, Monza, Italy

4. 4Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Japan

5. 5Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini, Genova, Italy

6. 6Division of Hematology/Oncology, Kanagawa Children's Medical Center, Yokohama, Japan

7. 7Department of Pediatrics, Seoul National University College of Medicine, Seoul, South Korea

8. 8Seoul National University Cancer Research Institute, Seoul, South Korea

9. 9Seoul National University Children's Hospital, Seoul, South Korea

10. 10Wide River Institute of Immunology, Hongcheon-gun, South Korea

11. 11Nationwide Children's Hospital, The Ohio State University, Columbus, OH

12. 12Pediatric Hematology/Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey

13. 13Department of Pediatric Oncology, Hematology and Stem Cell Transplantation, Hospital Niño Jesús, Madrid, Spain

14. 14Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

15. 15Groupe Hospitalier Pellegrin-Hôpital des Enfants, Bordeaux, France

16. 16Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

17. 17Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands

18. 18Unité d'Onco-Hématologie Pédiatrique, Centre d'Investigation Clinique (CIC) 1402 INSERM, Centre Hospitalier Universitaire (CHU) de Poitiers, Poitiers, France

19. 19Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA

20. 20Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL

21. 21Novartis Pharma AG, Basel, Switzerland

22. 22Novartis Pharmaceuticals Corporations, Munich, Germany

23. 23Intergrative and Innovative Hematology/Oncology Research Unit, Division of Hematology/Oncology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

Abstract

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 ∼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.

Publisher

American Society of Hematology

Subject

Hematology

Reference33 articles.

1. Diagnosis and treatment of chronic myeloid leukemia in 2015;Thompson;Mayo Clin Proc,2015

2. Management of chronic myeloid leukemia in children and adolescents: recommendations from the Children's Oncology Group CML Working Group;Athale;Pediatr Blood Cancer,2019

3. European Medicines Agency . Imatinib summary of opinion. 2013. Accessed 14 March 2023. https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-imatinib-accord_en.pdf.

4. Gleevec (imatinib). Prescribing information;Novartis Pharmacueticals,2022

5. FDA Approves Dasatinib for Pediatric Patients With CML;FDA,2017

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