Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcS-crizotinib trial - Institut Gustave Roussy
Article Dans Une Revue European Journal of Cancer Année : 2023

Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcS-crizotinib trial

1 AP-HP. Université Paris Saclay
2 IGR - Institut Gustave Roussy
3 U1018 (Équipe 2) - Oncostat
4 CESP - Centre de recherche en épidémiologie et santé des populations
5 SBE - Service de biostatistique et d'épidémiologie
6 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
7 UR - Université de Rennes
8 CHU Henri Mondor [Créteil]
9 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
10 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
11 UPD5 - Université Paris Descartes - Paris 5
12 CHU Reims - Hôpital universitaire Robert Debré [Reims]
13 URCA - Université de Reims Champagne-Ardenne
14 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
15 IHOPe - Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL]
16 CRCT - Centre de Recherches en Cancérologie de Toulouse
17 Institut Curie [Paris]
18 PSL - Université Paris Sciences et Lettres
19 CIC 1402 - CIC Poitiers – Centre d'investigation clinique de Poitiers
20 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
21 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
22 GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365
23 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
24 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
25 CHU La Réunion - Centre Hospitalier Universitaire de La Réunion
26 AP-HP - Hopital Saint-Louis [AP-HP]
27 UP11 - Université Paris-Sud - Paris 11
28 Institut Bergonié [Bordeaux]
29 CHU Trousseau [APHP]
30 SU - Sorbonne Université
31 TIMONE - Hôpital de la Timone [CHU - APHM]
32 INCa - Institut national du cancer
33 UNICANCER
David Sibon

Résumé

Background: The French phase II AcSé-crizotinib trial aimed to evaluate the safety and efficacy of crizotinib in patients with ALK, ROS1, and MET-driven malignancies, including ALK-positive anaplastic large-cell lymphoma (ALK ALCL). Methods - ALK ALCL patients 12 months or older with measurable disease and no standard care options available received crizotinib twice daily at 165 mg/m in children and adolescents and 250 mg in adults. The primary end-point was the response rate at 8 weeks. Results: Twenty-eight patients were enroled between February 2014 and March 2018. Three patients who were not treated were excluded from the analysis. The median age was 19 years. The median previous line of chemotherapy was two. In the 24 patients with an evaluable response, the response rate at 8 weeks was 67% (95% CI: 47-82%). All patients discontinued crizotinib after a median treatment duration of 3.7 months: eight for progression, two for adverse events (AEs) related to prior treatments, and 15 by choice, including six for allogeneic stem-cell transplantation. The median follow-up was 45 months. Nine patients experienced an event: eight relapses (seven after crizotinib discontinuation and one after dose reduction), and one died in complete remission. The median duration of response was 43.3 months (95% CI: 8.3-not reached). The 3-year progression-free and overall survival rates were 40% (95% CI: 23-59%) and 63% (95% CI: 43-79%). Grade 3 or 4 treatment-related AEs occurred in 32% of patients. Conclusion: Crizotinib shows efficacy and an acceptable safety profile in ALK ALCL relapsed/refractory patients. However, a large proportion of patients experience a relapse after crizotinib discontinuation. Future studies will assess if prolonged ALK inhibitor exposure has curative potential without consolidation.
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hal-04228222 , version 1 (09-04-2024)

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Laurence Brugières, Nathalie Cozic, Roch Houot, Charlotte Rigaud, David Sibon, et al.. Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcS-crizotinib trial. European Journal of Cancer, 2023, 191, pp.112984. ⟨10.1016/j.ejca.2023.112984⟩. ⟨hal-04228222⟩
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