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

TL;DR

Adults with a specific type of leukemia can achieve high survival rates using a pediatric-style chemotherapy and drug combo, without needing a stem cell transplant.

Contribution

A pediatric-inspired chemotherapy protocol with TKIs improves survival in Ph+ B-ALL adults without routine alloSCT.

Findings

Omitting asparaginase and routine alloSCT improved survival in Ph+ B-ALL patients.

The 2016–2019 cohort had 87.0% 4-year overall survival and 69.3% relapse-free survival.

Measurable residual disease guided treatment decisions and retained statistical significance.

Abstract

Tyrosine kinase inhibitors (TKIs) added to the pediatric-inspired Princess Margaret-Dana Farber Cancer Institute (PM-DFCI) chemotherapy protocol demonstrate that omitting asparaginase and routine allogeneic stem cell transplantation (alloSCT) in Philadelphia-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) significantly improves survival by reducing excess toxicity, provided that treatment decisions are guided by BCR::ABL1 measurable residual disease.

Tyrosine kinase inhibitors (TKIs) added to chemotherapy have improved outcomes of adult 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). In total, 141 patients (91.56%) achieved CR1. Patient outcomes improved iteratively, with the best results seen in the final (2016–2019) cohort: no asparaginase, no routine alloSCT referral in CR1; 4-year overall survival (OS) and relapse-free survival (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 measurable residual disease (MRD) was considered.

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