Frontline asciminib combination in CML patients

August 2023 EHA 2023 Andrea Enguita
Acute lymphoblastic leukemia, bone marrow smear, 3D illustration

During the 2023 European Haematology Association (EHA) congress, new combination strategies for the treatment of patients with chronic myeloid leukaemia were explored. In the frontline, the combination of asciminib with ATP-competing BCR:ABL1 inhibitors was associated with a high rate of deep molecular responses, but this came at the cost of considerable toxicity.

Recently approved as a third-line therapy for chronic myeloid leukaemia (CML) patients, the first-in-class BCR:ABL1 inhibitor, asciminib, is now being evaluated in the phase 2 FASCINATION study as a potential first-line treatment in combination with conventional ATP-competing tyrosine kinase inhibitors (TKIs) for newly diagnosed CML patients. The study objective was to improve the MR4 rate compared to standard therapy, potentially increasing the proportion of patients achieving treatment-free remission (TFR) over time.

Study findings

A total of 125 CML patients were assigned to one of four combinations: nilotinib 300 mg plus asciminib 20 mg, nilotinib 300 mg plus asciminib 40 mg, dasatinib 100 mg plus asciminib 80 mg, or imatinib 400 mg plus asciminib 60 mg, twice daily, based on the doctor’s choice (n=30, 32, 32, and 31, respectively). The primary endpoint was the MR4 at 12 months after the start of the treatment. At this point, 43 patients (38%) achieved MR4. Additionally, 77 patients (68%) achieved major molecular response (MMR), 25 patients (22%) achieved MR4.5, 9 patients (8%) achieved MR5, and 3 patients (3%) achieved MR5.5. Although the study was not powered sufficiently to detect statistical differences among the cohorts, the response rates were relatively similar, ranging from 32.1% of patients with MR4 at 12 months in cohort 1 (nilotinib plus asciminib 40 mg) to 42.9% in cohort 4 (imatinib plus asciminib). Grade 3-4 adverse events (AEs) were observed in 38% of patients during the first year, with a similar distribution among the cohorts. The most common grade 3-4 AEs included blood and lymphatic system disorders, followed by skin, gastrointestinal, cardiac, and metabolic toxicities. Within the first 12 months, a total of 21 patients discontinued the combination treatment due to, among others, skin and gastroenterological toxicities and treatment failure or disease progression.

In conclusion, combining asciminib with ATP-competing BCR:ABL1 inhibitors as a frontline treatment for CML patients was associated with a high rate of deep molecular response but this came at the cost of considerable toxicity. Further investigation with longer follow-up is planned to explore asciminib maintenance treatment after achieving deep molecular response and TFR.


Ernst T. Frontline asciminib combination in chronic phase chronic myeloid leukemia patients. the fascination trial. Presented at EHA 2023; Presentation ID S156.