Philadelphia Chromosome-Like ALL: NGS-Guided Targeted Therapy Strategies
This clinical review outlines evidence-based treatment approaches for Philadelphia chromosome-like acute lymphoblastic leukemia, a high-risk subtype whose diverse kinase-activating drivers have been unravelled through next-generation sequencing. The authors present illustrative vignettes covering newly diagnosed and relapsed/refractory cases in children, adolescents, and young adults, discussing JAK- and ABL-directed tyrosine kinase inhibitors alongside immunotherapy. Standard-of-care regimens remain undefined pending completion of ongoing clinical trials.
The original study
How I treat Philadelphia chromosome-like acute lymphoblastic leukemia in children, adolescents, and young adults.
- Authors
- Tran TH, Tasian SK
- Journal
- Blood
- Type
- Journal Article, Review, Case Reports, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.
- PMID
- 38657263
Original abstract
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) represents a high-risk B-lineage ALL subtype characterized by adverse clinical features and poor relapse-free survival despite risk-adapted multiagent chemotherapy regimens. The advent of next-generation sequencing has unraveled the diversity of kinase-activating genetic drivers in Ph-like ALL that are potentially amenable to personalized molecularly-targeted therapies. Based upon robust preclinical data and promising case series of clinical activity of tyrosine kinase inhibitor (TKI)-based treatment in adults and children with relevant genetic Ph-like ALL subtypes, several clinical trials have investigated the efficacy of JAK- or ABL-directed TKIs in cytokine receptor-like factor 2 (CRLF2)/JAK pathway-mutant or ABL-class Ph-like ALL, respectively. The final results of these trials are pending, and standard-of-care therapeutic approaches for patients with Ph-like ALL have yet to be defined. In this How I Treat perspective, we review recent literature to guide current evidence-based treatment recommendations via illustrative clinical vignettes of children, adolescents, and young adults with newly diagnosed or relapsed/refractory Ph-like ALL, and we further highlight open and soon-to-open trials investigating immunotherapy and TKIs specifically for this high-risk patient population.