A new study found asciminib to be a potentially safer and more effective treatment option for people with newly diagnosed chronic myeloid leukaemia (CML) when compared to current standard treatments with tyrosine kinase inhibitors (TKIs).

The research was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 31-June 4 in Chicago, Illinois.

The phase 3 ASC4FIRST clinical trial compared asciminib with available TKI therapies that are the current standard-of-care treatment for chronic phase CML.

A total of 405 patients with recently diagnosed chronic phase CML were randomly assigned to receive asciminib (201 patients) or an investigator selected TKI (204 patients). In the TKI arm, 102 patients received imatinib and 102 received a stronger second-generation TKI.

Investigators selected the TKI based on the overall health of the patient and patient preference. Typically, younger patients who did not have additional health concerns received treatment with a second generation TKI as they could tolerate more potent drugs better.

The median age of the participants was 52 years and 65% of the participants were men. Around 54% of the participants were White and 44% of the participants were Asian. Cancer centres in 29 countries enroled patients in this study.

Key Findings

• As of November 28, 2023, treatment was ongoing for 86% of the patients receiving asciminib, 62% of the patients receiving imatinib, and 75% of the patients receiving a second generation TKI.
• After 48 weeks, 68% of patients in the asciminib arm had achieved a major molecular response compared to 49% in the TKI arm (including both imatinib and second generation TKIs).
• A deep molecular response was observed in 39% of patients in the asciminib arm in comparison to 21% in the TKI arm. People who have a deep molecular response may eventually be considered in remission and could stop treatment.
• In a subset analysis, patients who were selected to receive imatinib but randomised to asciminib were compared to the imatinib arm, and 100 patients selected for a second generation TKI but randomised to asciminib were compared to the second generation TKI arm. A major molecular response was reached in 40% of the patients in the imatinib arm in comparison to 69% in the corresponding asciminib subset. In the second generation TKI arm, 58% of the patients reached a major molecular response compared to 66% in the corresponding asciminib subset.  

Most adverse events were fewer in the asciminib arm when compared to the TKI arm. The most frequent adverse events in the asciminib arm were low platelet count (13%) and low neutrophil count (10%).

Asciminib had a lower rate of discontinuation and lower rates of dose adjustment or treatment interruptions.

Treatment was most often discontinued because it did not work, or because of unwanted side effects. Finally, blood clots, a severe side effect of TKIs, were present in only 1% of the participants who took asciminib.

“This randomised trial demonstrated that asciminib achieved a statistically superior efficacy when compared to all TKIs available for newly diagnosed patients with chronic phase CML. Importantly, safety and tolerability of asciminib was also excellent. This combination of potency and safety may enable more patients to achieve treatment-free remission, the ultimate goal of CML therapy,” said lead study author Timothy Hughes, MD, from the South Australian Health and Medical Research Institute and University of Adelaide, Australia.   

“Asciminib demonstrated superior efficacy compared to current standard-of-care targeted therapies, and was accompanied by a more favourable safety profile with fewer adverse events, drug interruptions, and drug discontinuations. The excellent combination of efficacy and tolerability of asciminib versus current first-line treatments positions it to be a potential treatment choice for patients with chronic myeloid leukaemia.” – Oreofe O. Odejide, MD, MPH, Dana-Farber Cancer Institute, Boston, Massachusetts

Next Steps

Researchers will continue to follow the participants to understand the long-term safety profile of asciminib and to determine if reaching an MMR earlier continues to be a way to predict outcomes.

Additional studies will measure overall survival, progression-free survival, and if treatment-free remission is reached.  

Source: ASCO