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Response to tyrosine kinase inhibitors in myeloid neoplasms associated with PCM1-JAK2, BCR-JAK2 and ETV6-ABL1 fusion genes

We report on 18 patients with myeloid neoplasms and associated tyrosine kinase (TK) fusion genes on treatment with the TK inhibitors (TKI) ruxolitinib (PCM1-JAK2, n = 8; BCR-JAK2, n = 1) and imatinib, nilotinib or dasatinib (ETV6-ABL1, n = 9). On ruxolitinib (median 24 months, range 2-36 months), a...

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Hauptverfasser: Schwaab, Juliana (VerfasserIn) , Naumann, Nicole (VerfasserIn) , Lübke, Johannes (VerfasserIn) , Jawhar, Mohamad (VerfasserIn) , Somervaille, Tim C.P. (VerfasserIn) , Williams, Mark S. (VerfasserIn) , Frewin, Rebecca (VerfasserIn) , Jost, Philipp J. (VerfasserIn) , Lichtenegger, Felix S. (VerfasserIn) , La Rosée, Paul (VerfasserIn) , Storch, Nicola (VerfasserIn) , Haferlach, Torsten (VerfasserIn) , Horny, Hans-Peter (VerfasserIn) , Fabarius, Alice (VerfasserIn) , Haferlach, Claudia (VerfasserIn) , Burchert, Andreas (VerfasserIn) , Hofmann, Wolf-Karsten (VerfasserIn) , Cross, Nicholas C.P. (VerfasserIn) , Hochhaus, Andreas (VerfasserIn) , Reiter, Andreas (VerfasserIn) , Metzgeroth, Georgia (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2020
In: American journal of hematology
Year: 2020, Jahrgang: 95, Heft: 7, Pages: 824-833
ISSN:1096-8652
DOI:10.1002/ajh.25825
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ajh.25825
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.25825
Volltext
Verfasserangaben:Juliana Schwaab, Nicole Naumann, Johannes Luebke, Mohamad Jawhar, Tim C.P. Somervaille, Mark S. Williams, Rebecca Frewin, Philipp J. Jost, Felix S. Lichtenegger, Paul La Rosée, Nicola Storch, Torsten Haferlach, Hans-Peter Horny, Alice Fabarius, Claudia Haferlach, Andreas Burchert, Wolf-Karsten Hofmann, Nicholas C.P. Cross, Andreas Hochhaus, Andreas Reiter, Georgia Metzgeroth
Beschreibung
Zusammenfassung:We report on 18 patients with myeloid neoplasms and associated tyrosine kinase (TK) fusion genes on treatment with the TK inhibitors (TKI) ruxolitinib (PCM1-JAK2, n = 8; BCR-JAK2, n = 1) and imatinib, nilotinib or dasatinib (ETV6-ABL1, n = 9). On ruxolitinib (median 24 months, range 2-36 months), a complete hematologic response (CHR) and complete cytogenetic response (CCR) was achieved by five of nine and two of nine patients, respectively. However, ruxolitinib was stopped in eight of nine patients because of primary resistance (n = 3), progression (n = 3) or planned allogeneic stem cell transplantation (allo SCT, n = 2). At a median of 36 months (range 4-78 months) from diagnosis, five of nine patients are alive: four of six patients after allo SCT and one patient who remains on ruxolitinib. In ETV6-ABL1 positive patients, a durable CHR was achieved by four of nine patients (imatinib with one of five, nilotinib with two of three, dasatinib with one of one). Because of inadequate efficacy (lack of hematological and/or cytogenetic/molecular response), six of nine patients (imatinib, n = 5; nilotinib, n = 1) were switched to nilotinib or dasatinib. At a median of 23 months (range 3-60 months) from diagnosis, five of nine patients are in CCR or complete molecular response (nilotinib, n = 2; dasatinib, n = 2; allo SCT, n = 1) while two of nine patients have died. We conclude that (a) responses on ruxolitinib may only be transient in the majority of JAK2 fusion gene positive patients with allo SCT being an important early treatment option, and (b) nilotinib or dasatinib may be more effective than imatinib to induce durable complete remissions in ETV6-ABL1 positive patients.
Beschreibung:12 April 2020
First published: 12 April 2020
Beschreibung:Online Resource
ISSN:1096-8652
DOI:10.1002/ajh.25825

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