Latest Strategies for Treating Patients With Chronic Myeloid Leukemia

At the 2025 Lymphoma, Leukemia & Myeloma (LL&M) Winter Symposium in Miami, Florida, Fadi Haddad, MD, MD Anderson Cancer Center, Houston, Texas, discusses updates in strategies for the treatment of patients with chronic myeloid leukemia.

Transcript:

I am Fadi Haddad, a leukemia physician at the Department of Leukemia at the University of Texas, MD Anderson Cancer Center in Houston, and I'm happy to be here at the LL&M 2025 meeting in Miami to talk a little bit about the updates in chronic myeloid leukemia for 2024 and 2025.

I would like to share with you 3 updates, the first one in the frontline setting. The updated results from the ASC4FIRST trial demonstrated the superiority of asciminib, which is an allostatic inhibitor, over imatinib and second generation TKIs, in patients who are newly diagnosed with chronic myeloid leukemia.

The primary end point of the study was the rate of major molecular response (MMR) after 48 weeks of treatment, and asciminib demonstrated superiority in the MMR rate over both imatinib, second generation TKIs, and all TKIs combined in the frontline setting. This study led to the approval of asciminib as frontline treatment for patients with chronic myeloid leukemia in chronic phase.

The second study that I would like to highlight is the ASC2ESCALATE trial, which also evaluated asciminib, but now in the second-line setting. Here we had patients who received 1 previous line of therapy, they either have toxicity or they did not respond, or responded but lost their response, and therefore were switched to a second line treatment, which was asciminib in this case.

Patients who were treated with asciminib achieved a major molecular remission rate of about 43% after 6 months of treatment. We are still waiting for longer follow-up to meet the primary end point of the study, which is an MMR rate at 12 months. But results seem promising, particularly in the group of patients who didn't have disease resistance but have only side effects. The group of patients who had true disease resistance had lower rates of response.

Finally, I would like to highlight in the third-line setting and beyond, olverembatinib. Olverembatinib is a third-generation tyrosine kinase inhibitor that is approved in China for the treatment of patients with chronic myeloid leukemia who are relapsing after multiple lines of therapy. In our study that was conducted in the United States, it was a multicenter study, in patients who are heavily pretreated, 81% of them treated with 3 or more tyrosine kinase inhibitors, some of them have the T315I mutation.

Half of the patients were treated with ponatinib or asciminib, and even in this context, the complete cytogenetic response rate was in the range of 50% and the major molecular response rate was in the range of 40%. These results are very encouraging.

There is currently a randomized phase 3 trial comparing olverembatinib to bosutinib in the third line setting, and the results are eagerly awaited and hopefully they can lead to practice changing results by the introduction and the approval of olverembatinib in the salvage setting in the United States.

Source:

Haddad F. Updates in Chronic Myeloid Leukemia. Presented at Lymphoma, Leukemia & Winter Symposium; February 7-9, 2025. Miami, Florida.