Adult Patients with Philadelphia-Positive B-Cell Acute Lymphoblastic Leukemia Treated with a Pediatric-Inspired Multiagent Chemotherapy Regimen, in Combination with a TKI, Do Not Require Routine alloSCT

Tyrosine kinase inhibitors (TKIs) added to chemotherapy have improved outcomes ofadult patients with Philadelphia-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL). These improvements initially led to a larger proportion of patients realizing allogeneic stem cell transplantation (alloSCT), long considered essential for cure, but there has been a re-evaluation of alloSCT. At Princess Margaret Hospital (PM), adult patients with Ph+ B-ALL have been treated with a pediatric-inspired chemotherapy protocol with mostly imatinib. In the last two decades, we have witnessed many iterative changes in our approach. Here we examine the outcomes of all Ph+ B-ALL patients treated at our institution from 2001 to 2019. During this time, there were two major protocol changes – omission of asparaginase in 2009, and discontinuation of routine referral for first complete remission (CR1) alloSCT from the early 2010s. Median follow-up was 41.13 months (range, 0.46-228.79). 141 patients (91.56%) achieved CR1. Patient outcomes improved iteratively, with best results seen in the final (2016-2019) cohort: no asparaginase, no routine alloSCT referral in CR1; 4-year OS and RFS were 87.0% and 69.3%, respectively. The long-term OS in this patient group retained statistical significance in the multivariable analysis (p=0.0176) when BCR::ABL1 molecular residual disease (MRD) were considered.