ABL1 F317L

Mutational analysis is recommended to identify patients at risk of disease progression. Therefore, early detection of such mutations may allow timely treatment intervention to prevent or overcome resistance.

The present study demonstrated that a half of baseline conc ABPIs in combination with ASC is as effective as other ABPIs not just in WT but also in other ABL1 KDM CML cell lines. Different CML cell lines harboring different ABL KDM has different treatment spectrum on optimal ABPI drug as well as optimal drug conc. This result will be useful to design future clinical trial of dual blockade of ASC with other ABPIs considering the ABL KDM profiles.

This retrospective study had suggested promising effects of flumatinib, which showed induced high rates of CCyR and MMR or DMR in patients resistant or intolerant to imatinib. The incidence of AEs during flumatinib treatment was tolerable.

The 15 R/R patients (11, Ph + ALL; 4, CML-BP) received olverembatinib 30 or 40 mg on alternate days combined with VP (vindesine 4 mg once per week for 4 weeks and prednisone 1 mg/kg for 3 weeks and tapered at the fourth)...Among the 16 patients with molecular resistance to TKI-based chemotherapy (imatinib [n = 4]; dasatinib [n = 9]; flumatinib [n = 3]), 2 received olverembatinib monotherapy, 7 olverembatinib plus VP, and 7 hyper-CVAD, of whom 8 received subsequent allogeneic transplantation...Treatment-related nonhematologic severe adverse events were observed in 3 patients, including (each) stable angina pectoris, severe pneumonia, and fatal Klebsiella sepsis. Conclusions Olverembatinib-based chemotherapy is effective and safe in patients with R/R and molecular resistant Ph + ALL or CML-LBP.

He was treated with imatinib, nilotinib, and dasatinib, but failed to achieve a complete cytogenetic response (CCyR). Chronic renal failure may cause hyperabsorption and metabolic retardation in patients receiving PON. Initiation of hemodialysis may improve homeostasis resulting in enhanced anti-tumor immunity against CML.

Dasatinib in combination with a two-week vincristine and glucocorticoids regimen were administered, followed by sequential infusions of CD19 and CD22 CAR-T cells. Conclusions Dasatinib in combination with CAR-T cell therapy has enabled chemotherapy-free treatment in newly diagnosed Ph-positive ALL. This treatment is characterized by high complete molecular response, high long-term survival, low toxicity and short treatment cycles.

In summary, our newly developed assay can be used for kinase domain mutation analysis from clinical samples and with very good sensitivity of 2%, which is in a well-acceptable range of 1% to 3% and is available on commonly used the Ion Torrent platform. This ability of the assay in detecting low-level variants and even compound variants makes it very important for selection of appropriate TKIs for CML patients.

One patient had co-expression of e14a2 and e14a8 transcripts. The results identify candidate single nucleotide variants and co-expressed BCR-ABL1 transcripts in cellular resistance to imatinib.

P1, N=12, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2023 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Jun 2025

Ba/F3 cells expressing a range of the most prevalent on-target BCR::ABL1 resistance mutants indicated that with the exception of certain P-loop mutations and F317L, ELVN-001 maintained potency, including for the myristoyl pocket mutations A344P and P465S and was active against the M244V mutation, an ATP pocket mutation known to confer resistance to asciminib. This FIH study will evaluate dosing, safety, tolerability, PK profile, and preliminary efficacy of ELVN-001 in CP-CML with and without T315I mutation. Study sponsor: Enliven Therapeutics. NCT05304377 BCR::ABL, Chronic myeloid leukemia, Tyrosine kinase inhibitor, Phase I