TY - JOUR
T1 - Treatment de-escalation in Philadelphia chromosome–positive B-cell acute lymphoblastic leukemia
T2 - the emerging role of chemotherapy-free regimens
AU - Haddad, Fadi G.
AU - Sawyers, Jacki
AU - Short, Nicholas J.
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by an MD Anderson Cancer Center Support Grant (CA016672) and SPORE. N.J.S. was supported by the American Society of Hematology Junior Faculty Scholar Award in Clinical Research.
Publisher Copyright:
© The Author(s), 2023.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - The management of Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has witnessed major progress over the past two decades. Initially, the incorporation of the first-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) imatinib into intensive chemotherapy regimens improved outcomes compared with chemotherapy alone. The combinations of chemotherapy with second- or third-generation TKIs further improved outcomes, with higher rates of complete molecular remission (CMR) and superior survival. The combination of ponatinib plus chemotherapy resulted in durable remissions and prolonged long-term survival, even in patients who did not receive allogeneic stem cell transplantation (SCT). The promising results seen with later-generation TKIs have caused many to re-evaluate the role of allogeneic SCT for patients who achieve CMR with potent TKI regimens. Recently, the chemotherapy-free combinations of blinatumomab plus TKIs were shown to be safe and effective in newly diagnosed Ph-positive ALL, sparing patients the toxicities associated with intensive chemotherapy. In particular, encouraging early results have been seen with the combination of blinatumomab plus ponatinib, suggesting that this regimen may represent a chemotherapy-free and SCT-sparing strategy for patients with Ph-positive ALL. Herein, we discuss the current evidence for frontline therapies of Ph-positive ALL, the treatment de-escalation strategies over time, and the role of allogeneic SCT in view of the emergence of newer chemotherapy-free regimens using potent TKIs.
AB - The management of Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) has witnessed major progress over the past two decades. Initially, the incorporation of the first-generation BCR::ABL1 tyrosine kinase inhibitor (TKI) imatinib into intensive chemotherapy regimens improved outcomes compared with chemotherapy alone. The combinations of chemotherapy with second- or third-generation TKIs further improved outcomes, with higher rates of complete molecular remission (CMR) and superior survival. The combination of ponatinib plus chemotherapy resulted in durable remissions and prolonged long-term survival, even in patients who did not receive allogeneic stem cell transplantation (SCT). The promising results seen with later-generation TKIs have caused many to re-evaluate the role of allogeneic SCT for patients who achieve CMR with potent TKI regimens. Recently, the chemotherapy-free combinations of blinatumomab plus TKIs were shown to be safe and effective in newly diagnosed Ph-positive ALL, sparing patients the toxicities associated with intensive chemotherapy. In particular, encouraging early results have been seen with the combination of blinatumomab plus ponatinib, suggesting that this regimen may represent a chemotherapy-free and SCT-sparing strategy for patients with Ph-positive ALL. Herein, we discuss the current evidence for frontline therapies of Ph-positive ALL, the treatment de-escalation strategies over time, and the role of allogeneic SCT in view of the emergence of newer chemotherapy-free regimens using potent TKIs.
KW - BCR::ABL1
KW - blinatumomab
KW - chemotherapy
KW - ponatinib
KW - tyrosine kinase inhibitor
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U2 - 10.1177/20406207231151294
DO - 10.1177/20406207231151294
M3 - Review article
C2 - 36755897
AN - SCOPUS:85147454940
SN - 2040-6207
VL - 14
JO - Therapeutic Advances in Hematology
JF - Therapeutic Advances in Hematology
ER -