Is intensive chemotherapy and allogeneic stem cell transplantation mandatory for curing Philadelphia chromosome-positive acute lymphoblastic leukemia in young patients in the era of multitarget agents?

ABSTRACT

Introduction

The treatment outcomes for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have improved with various tyrosine kinase inhibitors (TKIs) and bispecific T-cell engagers. Although allogeneic stem cell transplantation (allo-SCT) is the standard treatment for young patients with Ph+ALL, its role remains debatable in the era of TKIs and blinatumomab.

Areas covered

There are some issues regarding Ph+ALL. First, do young patients require intensive chemotherapy (IC) in the era of multitarget agents? Second, which TKI is preferred for frontline therapy? Third, should allo-SCT be performed in patients achieving complete remission with ponatinib and IC? Fourth, can chemo-free treatment lead to a cure without allo-SCT? We searched relevant literature from the last 30 years on PubMed; reviewed the role of chemo-free therapies and combinations of ponatinib and IC; and assessed the necessity of allo-SCT in young patients with Ph+ALL.

Expert opinion

Allo-SCT may not be needed, even in young patients with Ph+ALL treated with ponatinib-based IC or combined ponatinib and blinatumomab as frontline therapy. When adopting a ponatinib-based chemo-minimized regimen for induction, allo-SCT is needed with posttransplant ponatinib maintenance. Continuous exposure to ponatinib at pre- or post-transplant is regarded as one of the most important factor for the success of treatment.

KEYWORDS:

• acute lymphoblastic leukemia
• allogeneic stem cell transplantation
• intensive chemotherapy
• Philadelphia chromosome
• ponatinib

Article highlights

• A tyrosine kinase inhibitor (TKI)-based chemo-free regimen is sufficient to induce complete remission (CR) in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).

• Chemo-free strategy with TKI can be used as an option to avoid induction mortality and increase the chance of receiving an allogeneic stem cell transplantation (allo-SCT).

• A good quality CR with a TKI-based chemo-free regimen may minimize transplant-related mortality in patients receiving allo-SCT.

• The desire to replace cytotoxic therapies with allo-SCT is growing with the availability of powerful TKIs and bispecific T-cell engagers.

• Among various TKIs, frontline ponatinib is preferred to first- or second-generation TKIs for covering the baseline T315I mutation and preventing the emergence of clones resistant to TKIs.

• Continuous exposure to ponatinib at pre- or post-transplant is regarded as one of the most important factors for the success of chemo-free treatment in patients with Ph+ALL.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

SK Sohn conceptualized, conducted research, and wrote the original draft. DW Baek contributed to writing, reviewing, and editing. JM Lee, HJ Cho, YE Jang., YJ Lee, and JH Moon revised the manuscript and contributed editing. All authors provided final approval of the version to be submitted.

Additional information

Funding

This paper was not funded.