Asciminib may ‘transform’ treatment paradigm for chronic myeloid leukemia
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CHICAGO — Asciminib demonstrated superior efficacy to standard first-line therapies for certain patients with newly diagnosed chronic myeloid leukemia, according to study results presented at ASCO Annual Meeting.
Asciminib (Scemblix, Novartis) also exhibited a favorable safety and tolerability profile compared with imatinib and other tyrosine kinase inhibitors, researchers reported.
“CML is a chronic condition and, [although] TKIs have transformed the treatment landscape, many newly diagnosed patients fail to meet molecular response goals and many discontinue or change treatment due to intolerance,” Timothy Hughes, MD, of South Australian Health and Medical Research Institute and University of Adelaide in Australia, told Healio. “There is a clear need for treatment options that offer efficacy and a tolerability profile that may be suitable for long-term care, and Scemblix could be this suitable alternative for patients.”
Background and methods
Five-year relative survival for patients with CML has tripled — from 22% in the mid-1970s to 70% for patients diagnosed in the past decade — due largely to the development of TKI therapies.
Nearly half of patients who start TKI treatment change therapy because of tolerability concerns or development of drug resistance, according to study background.
Others remain on TKI therapy for many years and, in some cases, for the rest of their lives. This highlights the need for additional highly effective therapies that will not compromise safety, according to investigators.
Asciminib is the first STAMP drug — an acronym that stands for Specifically Target in the ABL Myristoyl Pocket. It is designed to be highly specific — minimizing toxicity and adverse events — as well as highly potent.
Cortes and colleagues conducted the randomized phase 3 ASC4FIRST trial to compare asciminib with available TKI therapies used in standard treatment for Philadelphia chromosome-positive CML in chronic phase.
The analysis included 405 patients (median age, 52 years; 65% men; 54% white; 44% Asian) from 29 countries with recently diagnosed disease.
Researchers assigned 201 patients to 80 mg asciminib daily. The other 204 patients received investigator-selected TKI based on patient health and preference — half received imatinib and the other half received a stronger second-generation TKI.
Major molecular response at week 48 for asciminib vs. all investigator-selected TKIs, as well as between a and imatinib, served as primary endpoints.
Results
As of data cutoff, a majority of patients assigned to asciminib (86%), imatinib (62%) or second-generation TKI (75%) remained on treatment.
At 48 weeks, researchers reported a higher major molecular response rate with asciminib vs. any TKI (67.7% vs. 49%; P < .001) or vs. imatinib alone (69.3% vs. 40.2%; P < .001).
More than a third (38.8%) of patients assigned asciminib achieved deep molecular response, meaning they eventually could be considered in remission and stop treatment.
Safety analysis showed lower incidence of most adverse events in the asciminib group.
The most common adverse events among patients assigned asciminib included low platelet count (13%) and low neutrophil count (10%).
Fewer patients assigned asciminib discontinued treatment, needed dose adjustments or required treatment interruption.
Only 1% of patients treated with asciminib developed blood clots, a potentially severe side effect of TKI therapy.
Next steps and implications
Investigators will continue to follow study participants to better understand asciminib’s long-term safety profile, as well as to determine if reaching a major molecular response earlier can predict outcomes.
Analyses also will be conducted for PFS, OS and treatment-free remission.
ASC4FIRST is the first randomized head-to-head phase 3 study to compare a CML treatment with investigator-selected standard of care first- and second-generation TKIs already broadly approved for use.
The efficacy and safety outcomes suggest asciminib may allow more patients to achieve treatment-free remission, researchers concluded.
“Asciminib’s strong benefit-risk profile may transform the CML treatment paradigm,” investigator Jorge E. Cortes, MD, director of Georgia Cancer Center at Augusta University, said during a press conference.
Perspective
Back to TopOreofe O. Odejide, MD, MPH
This is a very important study.
Patients with chronic myeloid leukemia often have to be on treatment for prolonged periods, and more than 40% of patients newly diagnosed with CML fail to achieve major molecular response after a year of treatment. Others have to switch treatment due to adverse events.
So it is very striking to see a therapy in asciminib that has such a nice balance of efficacy and tolerability. Patients assigned asciminib required fewer discontinuations compared with those assigned other TKI. We also see higher rates of major molecular response with asciminib.
This is really poised to potentially change the management of first-line treatment for CML.
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Hughes TP, et al. Abstract LBA6500. Presented at: ASCO Annual Meeting; May 31-June 4, 2024.
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