Many patients with chronic myeloid leukemia (CML) experience good survival outcomes from therapy with tyrosine kinase inhibitors (TKIs). However, 40-50% of these patients may need to change therapy due to disease progression or recurrence. Importantly, TKIs have different mechanisms of action, and the treatment effect depends on matching the drug and mutation.
The ASCEMBL trial is a Phase 3, randomized, multicenter study designed to explore whether asciminib is safe and effective for patients with CML compared with a commonly used ATP-binding TKI (bosutinib) [31]. Asciminib is a BCR-ABL1, first-in-class specifically targeting ABL myristoyl pocket (STAMP) inhibitor that differs from TKIs in its mechanism of action and ability to overcome mutations associated with TKI resistance. Primary analyses indicated that major molecular response (MMR) with asciminib exceeded MMR with bosutinib (25.5% versus 13.2%), and results at 48 weeks consistently favored asciminib over bosutinib in efficacy and safety. Analysis of efficacy and safety outcomes at 96 weeks showed that MMR with asciminib exceeded MMR with bosutinib by 21.7%. These results are important, as providers will likely start prescribing this medication now that it is approved. The results from the DETERMINATION trial were presented by Paul G. Richardson, MD (Dana-Farber Cancer Institute, Massachusetts, USA) [32]. This is a randomized Phase 3 study in which patients with newly diagnosed multiple myeloma were randomly assigned to treatment with lenalidomide, bortezomib, and dexamethasone with and without an autologous stem cell transplant (ASCT), with all receiving lenalidomide maintenance until progression. The study showed that patients with ASCT had significantly better PFS than those without, but no difference in OS was observed. Subgroup analyses indicated less benefit of ASCT in African American participants, individuals with a body mass index higher than 25 kg/m2, and those with higher disease stages. Significantly more related hematologic adverse events of grade 3 and higher were reported in the ASCT arm (89.9%) compared with the no-ASCT arm (60.5%). In addition, ten patients with ASCT experienced acute myeloid leukemia or myelodysplastic syndrome compared with no patients in the group without ASCT. Patients in the ASCT arm also had reductions from baseline in their quality of life surrounding the period of transplant, but these decreases were transient and leveled off over time. This study showed that ASCT still has a place in the care of patients with multiple myeloma, but not necessarily as a frontline treatment. The trial findings come with a few caveats. The window of ASCT may be limited as the disease progresses and becomes more aggressive. In addition, the median age of a multiple myeloma diagnosis in the United States is 69 years, with 31.5% of diagnoses occurring in individuals aged 65 to 74.2. The DETERMINATION trial participants’ ages ranged from 18 to 65, representing a younger and healthier population.