David Snyder, MD, Acting Chair, City of Hope Department of Hematology & Hematopoietic Cell Transplantation, Duarte, California, who was not involved in the ASCEMBL study, commented on the promise of asciminib: “The hope is this drug would be able to overcome resistance to other tyrosine kinase inhibitors, because it works by a different mechanism of action. This phase III trial compares asciminib with bosutinib as third- or fourth-line therapy. Asciminib was superior to bosutinib based on the endpoints defined in the study. That is a positive finding, and it offers another choice for patients with CML who need a third- or fourth-line drug. The differences may not be that dramatic clinically, but the toxicity might be a little different.”
David Snyder, MD
Regarding which patients may benefit from this new treatment option, Dr. Snyder said: “It’s estimated that one-third of patients with CML need to make a change from the original tyrosine kinase inhibitor, and maybe 20% end up needing a second- or a third-line therapy. There are about 100,000 people in the United States who are in remission or taking therapies for CML, so about 20% in this situation require a third- or fourth-line drug. So, that is the magnitude. In addition, about 5,000 patients are newly diagnosed with CML in the United States per year.”
Dr. Snyder noted that the drug will probably be studied earlier in CML and perhaps in combinations. “There’s reason to hope that the therapy can be brought earlier into the sequence of treatment, maybe as a second- or even first-line therapy. Preclinical data demonstrate that using asciminib plus one of the standard tyrosine kinase inhibitors as initial tyrosine kinase inhibitor therapy is a promising strategy, as that combination shows deep molecular responses and prevents the emergence of resistance to tyrosine kinase inhibitors,” he said.
DISCLOSURE: Dr. Snyder reported no conflicts of interest.
Since the introduction of imatinib almost 18 years ago, similar next-generation tyrosine kinase inhibitors have been approved for chronic myeloid leukemia (CML), including dasatinib, nilotinib, bosutinib, and ponatinib. These drugs attack a similar target, making it more likely that resistance to...