Patients with chronic myeloid leukemia in chronic phase (CML-CP) who previously received two or more tyrosine kinase inhibitors (TKIs) treated with Scemblix (asciminib) continued to experience greater efficacy with a better safety profile/tolerability when compared with Bosulif (bosutinib) with a median 3.7-year follow-up, according to findings from the phase 3 ASCEMBL studypresented at the 2023 American Society of Hematology (ASH) Meeting and Exposition.
“Most patients with chronic phase CML on long-term TKI therapy do have the potential for long-term chronic health issues,” lead study author Dr. Michael Mauro, leader of the myeloproliferative neoplasms program and hematologist at Memorial Sloan Kettering Cancer Center, said in a presentation of the data. “And those with treatment failure of at least two prior TKIs face additional challenges, such as high frequency of resistance causing mutations as well as toxicity.”
“Now, results from the ASCEMBL trial demonstrated superior efficacy and favorable safety at 24 and 96 weeks with (Scemblix) versus (Bosulif) in these patients with chronic phase CML, previously treated with at least two TKIs,” said Mauro.
The major molecular response (MMR) rate for Scemblix (33.8%) at week 156 (end of study) continued to be higher than with Bosulif (10.5%). After adjusting for baseline, the difference for major cytogenic response was 23.2% The BCL-ABL1 ≤1% rate at week 156 in patients without the major cytogenic response of 23.2% at baseline continued to be higher when treated with Scemblix than Bosulif (43.0% vs 11.1%).
In terms of progression-free survival (PFS, the time a patient lives without their disease worsening) and overall survival (OS, the time a patient lives following treatment, regardless of disease status), the investigators found that the PFS rate at three years was 85.2% with Scemblix and was 84% with Bosulif. The five-year OS rate was 87.8% with Scemblix and was 89.7% with Bosulif.
A total of 233 patients in the study with CML-CP following at least prior TKIs, experiencing intolerance or lack of efficacy were randomized into the Scemblix cohort (156 patients) or Bosulif cohort (76 patients). Patients either received 40 mg of Scemblix twice daily or received 500 mg of Bosulif once daily.
The investigators noted that patients receiving Bosulif who met the treatment failure criteria could switch to Scemblix and were analyzed separately. Patients who were intolerant to Bosulif and discontinued the treatment could not switch to Scemblix.
Of the 28 patients who discontinued Bosulif because of lack of efficacy, 25 switched to Scemblix. Almost every patient who switched (96%) had previously received a BCL-ABL1 greater than 10% before switching. None of the switch patients achieved an MMR at or by week 48 after switching. At week 48, 24% of patients achieved BCL-ABL1 of no more than 10% and 8% achieved BCL-ABL1 of 1% or less.
At the end of study treatment cutoff date, there were 77 (49.4%) and 8 (10.5%) patients who were still receiving Scemblix and Bosulif, respectively. Patients who experienced beneficial activity after the end of the study, after investigator assessment, continued receiving the treatment posttrial.
Common reasons for discontinuation of treatments were because of the lack of efficacy in 40 patients (25.5%) receiving Scemblix and 28 patients (36.8%) receiving Bosulif.
Although Scemblix had a longer median duration of exposure (156. weeks) compared with Bosulif (30.5 weeks) the safety profile and tolerability of Scemblix demonstrated better results versus Bosulif, remaining consistent with prior analyses.
Two patients in the study discontinued treatments because of adverse events following the week 96 cutoff. One patient who had received Scemblix reported pregnancy and the other patient who had received Bosulif reported diarrhea. Rates of discontinuation were lower for Scemblix (8.3%) vs Bosulif (27.6%).
The most common (at least 10%) grade 3 or higher side effects for Scemblix versus Bosulif were thrombocytopenia (22.4% vs 9.2%), neutropenia (18.6% vs 14.5%), diarrhea (0% vs 10.5%) and increased alanine aminotransferase (0.6% vs 14.5%). Most of the side effects occurred within the first six months of treatment.
“During the survival follow-up, six deaths occurred with (Scemblix) due to CML in three patients and hemorrhagic stroke, multiple organ dysfunction syndrome and COVID-19 and one patient each. And three with (Bosulif) treatment, one due to CML, one respiratory distress and one due to COVID-19,” Mauro reported.
The safety profile for Scemblix in patients who switched treatments remained consistent when compared with patients receiving ascliminib during the randomized period. The most frequent (≥10%) grade ≥3 AEs were neutropenia (32.0%) and thrombocytopenia (24.0%). Eight percent of switch patients experienced AEs and discontinued treatment.
Since the week 96 cutoff, exposure-adjusted incidence rates of arterial occlusive events (AOEs) with Scemblix decreased from 3.0 to 2.2 per 100 patient years, and no new AOEs occurred with the respective drug, which emphasized that the risk of AOEs did not increase over time. No new mutations occurred for patients since the week 96 cutoff who discontinued treatment due to lack of efficacy or disease progression.
“By the end of study, newly emerging mutations did not change since week 96, occurring in 7.6% of patients with (Scemblix) and 2.6% with (Bosulif),” Mauro noted.
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