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

• Published in: Bone marrow transplantation (Basingstoke) Vol. 56; no. 5; pp. 1190 - 1199
• Main Authors: Hirschbühl, Klaus, Labopin, Myriam, Houhou, Mohamed, Gabellier, Ludovic, Labussière-Wallet, Hélène, Lioure, Bruno, Beelen, Dietrich, Cornelissen, Jan, Wulf, Gerald, Jindra, Pavel, Tilly, Hervé, Passweg, Jakob, Niittyvuopio, Riita, Bug, Gesine, Schmid, Christoph, Nagler, Arnon, Giebel, Sebastian, Mohty, Mohamad
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2021; Nature Publishing Group
• Subjects: 692/308/2779/109/1943; 692/699/1541/1990/283/2125; Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Bone marrow; Cancer; Cell Biology; Chromosomes; Dosage; Drug therapy; Hematology; Immunosuppressive agents; Inhibitor drugs; Inhibitors; Internal Medicine; Kinases; Leukemia; Lymphatic leukemia; Medicine; Medicine & Public Health; Patient outcomes; Philadelphia chromosome; Public Health; Relapse; Stem cell transplantation; Stem Cells; Toxicity; Transplantation; Tyrosine; Tyrosine kinase inhibitors; Europe; Germany
• ISSN: 0268-3369; 1476-5365; 1476-5365
• DOI: 10.1038/s41409-020-01173-x

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.