Have any strategies in Ph-like ALL been shown to be effective?

Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subset of B-cell ALL characterized by high rates of treatment failure. Unsatisfactory outcomes with frontline therapy in adults with Ph-like ALL have been observed irrespective of the employed regimen, including modern pediatric-inspired regimens. Notably, Ph-like ALL is not an uncommon entity in adults, and it?s prevalence extends to older patients with B-cell ALL. As the majority of Ph-like ALL cases harbor genetic alterations in kinases and/or cytokine receptors, the integration of tyrosine kinase inhibitors in newly diagnosed patients and poor early responders with Ph-like ALL has emerged as an area of active research with several ongoing clinical trials. Furthermore, the encouraging activity of novel therapies such as inotuzumab and blinatumomab in chemo-refractory B-cell ALL has promoted an interest in introducing these agents early in Ph-like ALL management, which may lead to improved cure rates with frontline therapies, sparing more adults from undergoing early allogeneic hematopoietic cell transplantation (HCT). Finally, the high relapse rate in patients with Ph-like ALL, does not necessary correlate with early minimal residual disease (MRD) response, raising the question of consolidation with allogenic HCT in all adults with Ph-like ALL in first complete remission irrespective of MRD response.

Automated summary

Ph-like ALL is a high-risk subset of B-cell ALL in adults with poor outcomes with frontline therapy. The majority of cases harbor genetic alterations in kinases and/or cytokine receptors, leading to active research on integrating tyrosine kinase inhibitors in newly diagnosed patients and poor early responders. New therapies such as inotuzumab and blinatumomab show promising activity in chemo-refractory B-cell ALL, sparking interest in introducing these agents early in Ph-like ALL management to improve cure rates with frontline therapies.