Comparison of asciminib (ASCEMBL) to ponatinib (OPTIC, 45-mg-dose cohort)
| . | Asciminib 40 mg twice daily, arm of ASCEMBL study15,17 . | Ponatinib 45 mg daily, dose adjusted from OPTIC trial13 . | Comment . |
|---|---|---|---|
| Number of patients | 157 | 92 | |
| Eligibility | ELN201324 treatment failure (61%) or intolerance (38%) | Intolerant or resistant to >2 TKIs and not in MR2 | |
| Exclusion criteria | Within 6 mo prior to starting study treatment of myocardial infarction, angina pectoris, coronary artery bypass graft, or clinically significant cardiac arrhythmias | Any history of myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, peripheral vascular disease, NYHA class III or IV congestive heart failure, or reduced left ventricular ejection fraction within 6 mo prior to enrollment, clinically significant cardiac arrhythmias within 6 mo | |
| Baseline features | |||
| ≥3 prior TKI lines | 48% | 53% | |
| Resistant to last TKI | 61% | 98% | Disparity in favor of ponatinib in highly resistant cases |
| Intolerant patients | 38% | 2% | Disparity in favor of asciminib in intolerant cases |
| MCyR at baseline | 29% | 35% | |
| CCyR at baseline | 10% | 0% | |
| KD mutations at baseline (non-T315I) | 13% | 44% | Lower rate of patients with KD mutations in ASCEMBL |
| >10% BCR::ABL1 | 62% | NA | |
| Cardiac risk factors | Not specified | 29% had 1, 5% had >1 | |
| Results | |||
| Follow-up | 19 mo | 32 months | |
| Still on study therapy | 57% | 47% | |
| Discontinuation due to toxicity | 6% | 17% | Consistent with better tolerance to asciminib than ponatinib |
| Discontinuation due to lack of efficacy | 24% | 19% | |
| MR2 by 12 mo | 42% | 44% (49% in non-T315I group) | |
| MR2 by 12 mo in patients in CHR or worse on prior TKI | NA | 27/54 (50%) | Note high response rate on ponatinib in highly resistant cohort |
| MR2 by 12 mo in patients who had a better response than CHR to prior TKI | NA | 14/28 (50%) | |
| MMR by 12 mo | 29% | NA – 34% “overall rate with latest follow-up” | |
| MMR by 6 mo in patients in MCyR at baseline | 40% | NA | |
| MMR by 6 mo in patients NOT in MCyR at baseline | 17% | NA | Suggestion from this data that asciminib response may be more dependent on the level of response to prior therapy than is the case for ponatinib |
| AOEs per 100 patient-years | 3.4 | 7.6 (year 1) 5.9 (year 2) | In the ponatinib cohort receiving 30 mg initially, AOE rates/100 patient-years were 3 (year 1) and 2 (year 2) |
| . | Asciminib 40 mg twice daily, arm of ASCEMBL study15,17 . | Ponatinib 45 mg daily, dose adjusted from OPTIC trial13 . | Comment . |
|---|---|---|---|
| Number of patients | 157 | 92 | |
| Eligibility | ELN201324 treatment failure (61%) or intolerance (38%) | Intolerant or resistant to >2 TKIs and not in MR2 | |
| Exclusion criteria | Within 6 mo prior to starting study treatment of myocardial infarction, angina pectoris, coronary artery bypass graft, or clinically significant cardiac arrhythmias | Any history of myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, peripheral vascular disease, NYHA class III or IV congestive heart failure, or reduced left ventricular ejection fraction within 6 mo prior to enrollment, clinically significant cardiac arrhythmias within 6 mo | |
| Baseline features | |||
| ≥3 prior TKI lines | 48% | 53% | |
| Resistant to last TKI | 61% | 98% | Disparity in favor of ponatinib in highly resistant cases |
| Intolerant patients | 38% | 2% | Disparity in favor of asciminib in intolerant cases |
| MCyR at baseline | 29% | 35% | |
| CCyR at baseline | 10% | 0% | |
| KD mutations at baseline (non-T315I) | 13% | 44% | Lower rate of patients with KD mutations in ASCEMBL |
| >10% BCR::ABL1 | 62% | NA | |
| Cardiac risk factors | Not specified | 29% had 1, 5% had >1 | |
| Results | |||
| Follow-up | 19 mo | 32 months | |
| Still on study therapy | 57% | 47% | |
| Discontinuation due to toxicity | 6% | 17% | Consistent with better tolerance to asciminib than ponatinib |
| Discontinuation due to lack of efficacy | 24% | 19% | |
| MR2 by 12 mo | 42% | 44% (49% in non-T315I group) | |
| MR2 by 12 mo in patients in CHR or worse on prior TKI | NA | 27/54 (50%) | Note high response rate on ponatinib in highly resistant cohort |
| MR2 by 12 mo in patients who had a better response than CHR to prior TKI | NA | 14/28 (50%) | |
| MMR by 12 mo | 29% | NA – 34% “overall rate with latest follow-up” | |
| MMR by 6 mo in patients in MCyR at baseline | 40% | NA | |
| MMR by 6 mo in patients NOT in MCyR at baseline | 17% | NA | Suggestion from this data that asciminib response may be more dependent on the level of response to prior therapy than is the case for ponatinib |
| AOEs per 100 patient-years | 3.4 | 7.6 (year 1) 5.9 (year 2) | In the ponatinib cohort receiving 30 mg initially, AOE rates/100 patient-years were 3 (year 1) and 2 (year 2) |
Data reproduced with permission from Cortes et al,13 Réa et al,15 and Mauro et al.17
CCyR, complete cytogenetic response; CHR, complete hematologic response; NA, not available; NYHA, New York Heart Association.