Chronic Myeloid Leukemia: Therapy: TFR Failure, Resistance, and New Drug Development
Dennis Dong Hwan Kim, et al.
The Abstract concludes: These preliminary results suggest that rechallenge with DA after failing a first IM discontinuation attempt for TFR is well tolerated and effective as most cases rapidly regained at least MR4. However, more strict criteria should be considered for TFR2 attempt, including achievement of a 5.5 log reduction or deeper in BCR-ABL1 qPCR levels prior to the 2nd TKI discontinuation attempt, and a MR4 duration of more than 12 months.
Jorge E. Cortes, et al.
The Abstract concludes: Early results from DASCERN show that pts with suboptimal responses to imatinib at 3 mo who switched to dasatinib had a significantly increased rate of MMR at 12 mo compared to pts who remained on imatinib. Longer follow-up is required to assess the impact of early switching on PFS and OS, and achievement of deep molecular responses.
789 Compound BCR-ABL1 Kinase Domain Mutants: Prevalence, Spectrum and Correlation with Tyrosine Kinase Inhibitor Resistance in a Prospective Series of Philadelphia Chromosome-Positive Leukemia Patients Analyzed By Next Generation Sequencing
Simona Soverini, et al.
The Abstract concludes: Our results in a large unselected series of TKI-resistant pts analyzed by NGS show that:
- CMs are relatively infrequent in CP-CML, but may be a relevant issue in AP/BP-CML and Ph+ ALL;
- among pts with multiple mutations, those who have failed 1 line of therapy have most often polyclonality, whereas those who have failed ≥2 lines of therapy may have CMs or polyclonality;
- in vitro predictions of sensitivity and insensitivity based on IC50 data should be regarded with caution. In particular, the only compound mutant that we consistently found to be associated with ponatinib failure was the T315I+E255V.
Supported by EUTOS 2016.
Anna G Turkina, et al.
The Abstract concludes: MTD of PF-114 is 600 mg with skin toxicity as the DLT. The best safety/efficacy ratio was seen at doses of 200 and 300 mg which are being studied in expanded cohorts and soon in a phase-2 study.
Qian Jiang, et al.
The Abstract concludes: The preliminary results of the phase 1 study showed that HQP1351, a novel 3rd-generation TKI, is safe and highly active in treatment of the TKI-resistant patients with CP-CML and AP-CML,with or without T315I mutation.
Delphine Rea, et al.
The Abstract concludes: Overall, asciminib 200 mg BID monotherapy showed a favorable safety profile and clinical efficacy in PON-naive and PON-R/I pts carrying the T315I mut. This cohort will be expanded to enroll additional pts carrying the T315I mut. Asciminib may represent a new option for pts with CML and the T315I mut who are not eligible for PON or have failed PON treatment.