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), a complete hematologic remission (CHR) and complete cytogenetic remission (CCR) was achieved by 5/9 and 2/9 patients, respectively. However, ruxolitinib was stopped in 8/9 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) from diagnosis, 5/9 patients are alive: 4/6 patients after allo SCT and one patient who remains on ruxolitinib. In ETV6-ABL1 positive patients, a durable CHR was achieved by 4/9 patients (imatinib 1/5, nilotinib 2/3, dasatinib 1/1). Because of inadequate efficacy (lack of hematological and/or cytogenetic/molecular response), 6/9 patients (imatinib, n=5; nilotinib, n=1) were switched to nilotinib or dasatinib. At a median of 23 months (range 3-60) from diagnosis, 5/9 patients are in CCR or complete molecular remission (nilotinib, n=2; dasatinib, n=2; allo SCT, n=1) while 2/9 patients have died. We conclude that i) 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 ii) nilotinib or dasatinib may be more effective than imatinib to induce durable complete remissions in ETV6-ABL1 positive patients. This article is protected by copyright. All rights reserved.