ESH ALL 2021 | TKI use in Ph+ and Ph-like ALL
Stephen Hunger, MD, The Children’s Hospital of Philadelphia, Philadelphia, PA, discusses the use of tyrosine kinase inhibitors (TKIs) in Philadelphia chromosome-positive (Ph+) and Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL). It is now accepted that TKIs are critical in the treatment of Ph+ ALL. More recently, a high-risk subgroup of B-ALL known as Ph-like ALL was identified. Clinically, these patients are similar to Ph+ ALL; they have high white blood cell counts, poor early response, and low cure rates with standard therapy. In a subset of Ph-like ALL patients, fusions involving ABL1, ABL2, CSF1R, or PDGFRB are common and inhibited by the same ABL-class TKIs. Therefore, there is a great interest in treating patients with chemotherapy plus imatinib or dasatinib, as in Ph+ ALL, to improve outcomes. This interview took place during the 2021 European School of Hematology (ESH) 2nd Translational Research Conference on Acute Lymphoblastic Leukemia.
Transcript (edited for clarity)
I think it’s now well-accepted the TKI therapy is critical in the treatment of Philadelphia chromosome-positive ALL. It’s an integral part of therapy for patients of all ages. It has really helped to substantially improve outcomes since this was first started now almost two decades ago.
One of the other recently identified genetic subtypes in ALL is Philadelphia chromosome-like ALL...
I think it’s now well-accepted the TKI therapy is critical in the treatment of Philadelphia chromosome-positive ALL. It’s an integral part of therapy for patients of all ages. It has really helped to substantially improve outcomes since this was first started now almost two decades ago.
One of the other recently identified genetic subtypes in ALL is Philadelphia chromosome-like ALL. A subset of these cases have fusions involving one of about a half a dozen genes we refer to as ABL-class chains. The main ones are ABL-1, ABL-2, CSF1R, and PDGFR-beta. Clinically, these patients are similar to Ph-positive ALL, in that they have high white counts or early response and low cure rates with standard therapies. In vitro, these fusions really behave like BCR-ABL. They can induce growth factor independence. They are inhibited by the same ABL-class tyrosine kinase inhibitors as BCRA. There’s great interest in treating these patients with chemotherapy. Plus, most commonly, imatinib or dasatinib, as in Ph-positive ALL, to see if that improves outcome.
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Disclosures
Dr Hunger has received honoraria from Amgen and Servier, consulting fees from Novartis and owns common stock in Amgen.
