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CHICAGO -- The STAMP inhibitor asciminib (Scemblix) had a statistically superior response rate compared with investigator-selected tyrosine kinase inhibitors (TKIs) for patients with newly diagnosed chronic myeloid leukemia (CML), the phase III ASC4FIRST trial showed.

After 48 weeks of treatment, 67.7% of patients who received asciminib had achieved a major molecular response compared with 49% of those who received either first-generation imatinib or a second-generation TKI (P<0.001), reported Jorge E. Cortes, MD, of the Georgia Cancer Center at Augusta University, during a press briefing in advance of the American Society of Clinical Oncology (ASCO) annual meeting.

Looking at a stratified subgroup of patients who received asciminib versus those who received imatinib showed major molecular response rates of 69.3% and 40.2%, respectively (P<0.001).

A deep molecular response at 48 weeks was observed in 38.8% of patients in the asciminib arm compared with 20.6% in the investigator-selected TKI arm. There were also fewer adverse events (AEs) reported with asciminib, as well as lower rates of treatment discontinuation and dose adjustments or interruptions.

"This is the first study that compares a new drug -- in this case, asciminib -- to any of the tyrosine kinase inhibitors that are approved for this setting, frontline CML chronic phase," said Cortes. "The strong benefit-risk profile may change ... the treatment paradigm in chronic myeloid leukemia."

As ASCO discussant Oreofe O. Odejide, MD, MPH, of the Dana-Farber Cancer Institute in Boston, explained, "these patients with chronic myeloid leukemia often have to be on treatment for a very prolonged period. More than 40% of patients newly diagnosed with CML still fail to achieve a major molecular response after a year on treatment, and several also have to switch treatments because of adverse events."

"So it is really striking that we have a therapy that has a nice balance of efficacy and tolerability," she said. "This is really poised to potentially change the management of first-line treatment of chronic myeloid leukemia."

The FDA granted accelerated approval to asciminib in 2021 for the treatment of patients with Philadelphia chromosome (Ph)-positive CML in chronic phase who were previously treated with two or more TKIs.

included a total of 405 patients with newly diagnosed Ph-positive CML in chronic phase who had received no prior TKIs. Before randomization to the two arms, patients were selected to receive either imatinib or a second-generation TKI -- nilotinib (Tasigna), dasatinib (Sprycel), or bosutinib (Bosulif) -- depending on the overall fitness of the patient, as well as patient preference.

In total, 201 patients received asciminib and 204 received an investigator-selected TKI (102 with imatinib).

While the characteristics between groups were generally well balanced, Cortes noted that when imatinib was pre-selected as the treatment of choice, patients "tended to be a little bit older, whereas the patients who were pre-selected to receive a second-generation TKI ... were a little bit younger, showing perhaps the selection of imatinib is older patients just because of the risk of arterial-occlusive events, and these kinds of things."

At data cutoff, treatment was ongoing in 86.1% of patients in the asciminib arm versus 68.6% of those treated with investigator-selected TKIs.

While there were more cases of grade ≥3 thrombocytopenia in the asciminib arm compared with the imatinib patients (13% vs 6.1%), the incidence of other hematologic AEs (any grade or grade ≥3) with asciminib was either equivalent or less than that observed with investigator-selected TKIs. The same was true for non-hematologic toxicity.

The rate of arterial-occlusive events was 1% in the asciminib arm compared with 0% with imatinib and 2% with second-generation TKIs.

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