Second- and third-generation tyrosine kinase inhibitors for Philadelphia-positive adult acute lymphoblastic leukemia relapsing post allogeneic stem cell transplantation—a registry study on behalf of the EBMT Acute Leukemia Working Party

Klaus Hirschbühl, Myriam Labopin, Mohamed Houhou, Ludovic Gabellier, Hélène Labussière-Wallet, Bruno Lioure, Dietrich Beelen, Jan Cornelissen, Gerald Wulf, Pavel Jindra, Hervé Tilly, Jakob Passweg, Riita Niittyvuopio, Gesine Bug, Christoph Schmid*, Arnon Nagler, Sebastian Giebel, Mohamad Mohty

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Second- and third-generation tyrosine kinase inhibitors (TKI) play an important role in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, data on feasibility and efficacy of using these drugs for persisting or relapsed Ph + ALL after allogeneic stem cell transplantation (alloSCT) are scarce. Based on the EBMT Acute Leukemia Working Party registry, we evaluated the use of second-/third-generation TKI in 140 patients with Ph + ALL, suffering from measurable residual disease (MRD, n = 6), molecular relapse (MRel, n = 23), or hematological relapse (HRel, n = 111) following alloSCT. Treatment included dasatinib in 104, nilotinib in 18, or ponatinib in 18 patients. Forty-nine patients received TKI monotherapy, while 91 received additional treatment. Toxicity of second-/third-generation TKI post alloSCT was comparable to pretransplant use and could be managed with dose reduction or temporary discontinuation. Response rates were 71% (overall) and 61% (following TKI monotherapy). For the entire cohort, 2- and 5-year overall survival (OS) was 49% and 33%, respectively. OS was comparable among patients treated for persisting MRD/MRel and HRel. Among patients treated with TKI monotherapy, 2- and 5-year OS was 38% and 33%, respectively. The data underscore that second-/third-generation TKI are important compounds for the management of active Ph + ALL post alloSCT.

Original languageEnglish
Pages (from-to)1190-1199
Number of pages10
JournalBone Marrow Transplantation
Volume56
Issue number5
Early online date9 Dec 2020
DOIs
Publication statusPublished - May 2021

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