Asciminib Demonstrates Favorable Safety and Tolerability for Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase Compared With Tyrosine Kinase Inhibitor Therapy
Asciminib demonstrated favorable safety and tolerability compared with investigator-selected tyrosine kinase inhibitors (IS TKI) for the frontline treatment of chronic myeloid leukemia (CML) in chronic phase, according to results from a phase 3 study presented by Jorge Cortes, MD, Georgia Cancer Center, Augusta University, Augusta, Georgia at the 66th ASH Annual Meeting in San Diego, California.
The standard of care for CML has been tyrosine kinase inhibitors, including imatinib, nilotinib, dasatinib, and bosutinib. However, less than half of patients meet discontinuation criteria on standard TKI therapy and have a lower quality of life.
Researchers conducted a phase 3 study, the ASC4FIRST trial, to evaluate the safety and tolerability of asciminib against standard TKI therapy.
“In ASC4FIRST, asciminib had a better benefit-risk profile compared with IS TKIs,” Cortes and colleagues concluded, adding, “asciminib’s superior efficacy vs all IS TKIs, and more favorable safety/tolerability compared with each IS TKI (IMA, NIL, DAS, and BOS) suggests that ASC may transform the CML [treatment] paradigm.”
Transcript:
Hello, my name is Jorge Cortes from the Georgia Cancer Center at Augusta University, and I presented today the results of the ASC4FIRST study. What this was, was the 96-week data, representing a secondary end point of this study.
As a background, asciminib has shown significant activity in patients with prior therapy, with very good efficacy and very good safety profile. And because of that high efficacy and the very good safety profile, we decided that it was important to test it as initial therapy. This study was designed for patients with chronic phase CML that had not received any prior therapy, and they were randomized to receive either asciminib or any of the approved therapies, any of the approved tyrosine kinase inhibitors for initial therapy that included imatinib or any of the second generation TKIs.
Prior to randomizations, the physicians and the patients had to decide, if randomized to the control arm, whether they would go to the imatinib or to a second generation TKI. We had 2 strata: the imatinib strata, the second generation TKI strata. The primary end point, the primary efficacy results of 48-weeks, rate of major molecular response. There were 2 primary endpoints, asciminib versus any of the tyrosine kinase inhibitors and asciminib versus imatinib. Both primary end points were met, that led to the approval of asciminib for frontline therapy in the US and we are doing the same analysis now with 96 weeks of follow-up.
What these results showed was that the difference in favor of asciminib persisted, or actually increased, with an additional 48 weeks of follow-up. By 96 weeks, in comparison to any of the tyrosine kinase inhibitors, and in comparison, with imatinib, there was a statistically significant difference. The differences actually increased the delta between the rate of major molecular response with the control and with asciminib increased. It was also true in the comparison versus the second generation TKI. Although the study is not powered for this particular comparison, the rate of response actually almost doubled in favor of asciminib. That is very, very good.
We also looked at the rates of MR ([molecular response]) 4s and MR 4.5s—all of these continue to be better and actually increased over time in favor of asciminib versus all TKIs, versus imatinib, and versus second generation TKI. In terms of safety profile, we continue seeing many more grade 3 adverse events with imatinib, and particularly with second generation TKIs compared to asciminib.
Far fewer treatment discontinuations because of adverse events with asciminib compared to both imatinib and second generation TKIs, 5% versus about 13% with each one of these other cohorts. Far fewer treatment interruptions and those reductions with asciminib compared to imatinib and particularly second generation TKIs, the rate of adverse events is equal or lower for most of them, for asciminib compared to either imatinib or with second generation TKIs.
Even some of the adverse events that are the ones that are more common with asciminib, for example, lipase elevation is more common actually seen in this study with the second-generation TKIs, there's been only 1 additional arterial occlusive event with asciminib and one additional one with second generation TKIs. The rate continues to be very low, only 4 and 3 patients total for asciminib and second generation TKIs, overall, maintaining a very good safety profile.
The results essentially show that the treatment with asciminib results [had] very good results in efficacy, better efficacy compared to both imatinib and all TKIs, and better safety profile for asciminib. It justifies that the asciminib becomes a very good standard of care for patients with newly diagnosed chronic myeloid leukemia in the chronic phase.
Source:
Cortes JE, Hochhaus A, Hughes TP, et al. Asciminib (ASC) demonstrates favorable safety and tolerability compared with each investigator-selected tyrosine kinase inhibitor (IS TKI) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) in the pivotal phase 3 ASC4FIRST study. Dec 7-10, 2024; San Diego, CA. Abstract: 475