A review published in JAMA Oncology (online June 21, 2018; doi:10.1001/jamaoncol.2018.1915) sheds light on the importance of therapies targeting specific transcripts or leukemic cell surface antigens in the treatment of adults with acute lymphoblastic leukemia (ALL).
Within the past 40 years, there has been “remarkable progress” in the understanding of the pathophysiology and in developing improved personalized therapies for adults with acute ALL, according to Elias Jabbour, MD, department of leukemia, The University of Texas MD Anderson Cancer Center, and colleagues.
In an attempt to better describe the progress in this disease, Dr Jabbour and colleagues searched MEDLINE, the American Society of Clinical Oncology, and American Society of Hematology websites for published literature containing the search terms “acute lymphoblastic or lymphocytic leukemia” or “ALL.” Selected publications for data analysis were mostly published within the past 5 years, but researchers did not exclude commonly referenced or highly regarded older publications.
The literature review showed that targeted therapies toward specific transcripts—including BCR-ABL1 tyrosine kinase oncoprotein by tyrosine kinase inhibitors—and specific leukemic cell surface antigens—including CD20, CD22, and CD19 monoclonal antibodies—are considered major breakthroughs.
Current treatments, researchers continued, produce long-term survival in 50% of patients with precursor B-cell ALL – including up to 70% with Philadelphia chromosome (Ph)-positive disease, up to 60% with T-cell disease, and 80% with mature B-cell disease.
Dr Jabbour and colleagues acknowledged the role of next-generation sequencing and genomic profiling in identifying new prognostic markers, targets, and ALL subtypes, such as Ph-like ALL.
The future of adult ALL treatment has been shaped by monoclonal antibodies, bispecific antibody constructs, and chimeric antigen receptor T-cell therapies developed and approved by the Food and Drug Administration in the past 7 years, researchers noted. Approvals of blinatumomab in 2014, inotuzumab in 2017, and tisagenlecleucel in 2017 as salvage therapies are now being investigated in combined modalities as salvage and frontline therapies.
“The incorporation of new monoclonal antibodies and other targeted approaches into frontline regimens is showing promising results,” researchers concluded. “If confirmed, such strategies may increase the cure rates in adults to levels achieved in pediatric ALL and reduce the need for intensive and prolonged chemotherapy.”—Zachary Bessette