Dasatinib plus prednisone as induction and consolidation for adults with Ph‐positive acute lymphoblastic leukaemia: A single‐arm, multicentre, phase 2 trial

Abstract

SummaryTo reducing chemotherapy‐related toxicity, the chemo‐free regimens become a new trend of Ph + ALL treatment. Therefore, we conducted a phase 2 trial of dasatinib plus prednisone, as induction (Course I) and early consolidation (Courses II and III) treating newly diagnosed Ph + ALL. The trial was registered at www.chictr.org.cn, ChiCTR2000038053. Forty‐one patients were enrolled from 15 hospitals. The complete remission (CR) was 95% (39/41), including two elderly induction deaths. By the end of Course III, 25.6% (10/39) of patients achieved a complete molecular response. With a median follow‐up of 15.4 months, 2‐year disease‐free survival (DFS) were 100% and 33% for patients who receiving haematopoietic stem cell transplantation (HSCT) at CR1 and receiving chemotherapy alone respectively. When censored at time of HSCT, 2‐year DFS were 51% and 45% for young and elderly patients (p = 0.987). 2‐year overall survival were 45%, 86% and 100% for patients without HSCT, receiving HSCT after relapse and receiving HSCT at CR1 respectively. A total of 12 patients had marrow recurrences and one had CNS relapse, with 38% occurred early (between Courses I and III). IKZF1 gene deletion was shown to be associated with relapse (p = 0.019). This chemo‐free induction and early consolidation regimen was efficacious and well‐tolerated in de novo Ph + ALL. Allogeneic HSCT conferred definite survival advantage after chemo‐free induction.

Moving away from chemotherapy in newly diagnosed Philadelphia chromosome‐positive B‐cell acute lymphoblastic leukaemia

“…Twelve other patients had a bone marrow relapse, all of whom had acquired a T315I mutation, and one patient had a central nervous system (CNS) relapse. 8 Findings from these studies suggest that the combinations of corticosteroids plus TKIs are feasible in patients with newly diagnosed Ph-positive ALL. However, they result in inferior CMR and long-term survival rates compared with intensive chemotherapy combinations and are likely not sufficient alone for most patients without proper consolidation strategies.…”

“…5 In their paper, the authors report the results of the combination of dasatinib plus prednisone in adults with Ph-positive ALL. 8 In this study, 41 patients with a median age of 53 years (range, 16-84 years) were treated with dasatinib plus prednisone as induction (Cycle 1) and consolidation (Cycles 2-3). Thirty (73%) patients had p190 transcript and nine (30%) had IKZF1 deletion.…”