SOHO 2025 | The management of Ph-like ALL: moving towards an individualized precision medicine approach
Sarah Tasian, MD, Children’s Hospital of Philadelphia, Philadelphia, PA, comments on the potential value of an individualized precision medicine approach for the management of Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL). Dr Tasian outlines which patient subgroups may benefit from specific agents, based on the presence of common mutations. This interview took place at the 13th Annual Meeting of the Society of Hematologic Oncology (SOHO 2025) in Houston, TX.
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Transcript
So the Philadelphia chromosome-like or Ph-like subtype of ALL is now known to be a pretty common subtype, and we know that patients do very poorly with conventional chemotherapy. So there’s been a lot of interest in trying to introduce precision medicine therapeutics, particularly targeting aberrant kinases, as well as trying to understand the therapeutic potential of antibody-based immunotherapy such as blinatumomab to try to improve those outcomes...
So the Philadelphia chromosome-like or Ph-like subtype of ALL is now known to be a pretty common subtype, and we know that patients do very poorly with conventional chemotherapy. So there’s been a lot of interest in trying to introduce precision medicine therapeutics, particularly targeting aberrant kinases, as well as trying to understand the therapeutic potential of antibody-based immunotherapy such as blinatumomab to try to improve those outcomes.
I think right now for the patients with the ABL class subtype of Ph-like ALL, we’re very interested in adding TKIs to their therapy. And based on the remarkable successes also in patients with Ph-positive ALL, trying to understand how we can best now add blinatumomab to the frontline therapies and combine those safely with TKIs. In the pediatric space, we have recently learned through preclinical studies that using fusion-specific TKI selection is probably quite important. So for the patients who have the PDGFR beta fusions, we think that these patients respond preferentially better to imatinib, whereas those with ABL1, ABL2, or CSF1R fusions respond better to second-generation TKIs such as dasatinib and potentially bosutinib. We are very interested, I think, from some of the emerging adult data with third-generation TKI, such as ponatinib, as potentially being superior across-the-board in ABL class Ph-like ALL. That remains for us in pediatrics still to be understood. And then with respect to the CRLF2 JAK class of patients, we’ve conducted many clinical trials both in the pediatric and the adult space looking at the JAK inhibitor ruxolitinib, the data are still pending and we don’t quite yet know if that is necessary for these patients or using things like blinatumomab or inotuzumab in the front line may be sufficient.
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