632. Chronic Myeloid Leukemia: Therapy: Response Monitoring and Prognosis


Conclusion cited from the abstract: 

- Mutation testing in the Failure setting aims to a timely and rational TKI switch. The incidence of low level mutations relevant to the selection of subsequent-line therapy and the TAT of routine NGS in our cohort suggest that multiplex ddPCR would be an easier and faster alternative.

- Mutation testing in the Warning setting may identify pts who need a change in therapy rather than a ‘watch and wait’ approach. In our cohort, approx 1/5 of the Warning pts negative by Sanger seq had low level mutations resistant to the TKI they were receiving, that ultimately led to Failure. Earlier detection of emerging resistant mutations enabled by NGS (or by ddPCR in pts receiving 2GTKIs) should support proactive TKI switch.




Conclusion cited from the abstract: Enhanced bioinformatic analysis of RNAseq data has revealed a high proportion of pts with truncating mutations in cancer genes indicated by novel RNA splicing (27% pts in BC). Using RNA-based sequencing allows an evaluation of the potential functional effect of variants that are not apparent by DNA-based mutation analysis. We suggest that future studies include RNA sequencing to detect a broader spectrum of mutations associated with TKI resistance.




Timothy P. Hughes, et al. 

Conclusion cited from the abstract: We have constructed a predictive model for DMR achievement for pts who receive optimised frontline imatinib therapy. This model performs better than combining ELTS and 3-mths BCR-ABL1%. We postulate that this predictive model could enable identification of poor risk pts at 3 mths who would benefit from intensified therapeutic approaches to obtain eligibility for TFR and potentially optimal clinical outcome.




Conclusion cited from the abstract: This is the first prospective trial to demonstrate that NGS can detect low level KD mutations in CP CML patients treated with first line 2GTKI±Peg-IFN after only 3 to 6 months on therapy before these become detectable by SS and despite achieving an optimal response in BCR-ABL transcript level reduction (according to ELN 2013). The proportion of patients who develop KD mutations by 12 months on upfront 2GTKI should not be underestimated, as their outcome is poor. NGS may trigger early clinical intervention and prevent progression in this group, although a prospective trial is needed in this regard. Finally, the proportion of KD incidence in pts who receive Peg-IFN in addition to nilotinib might be lower compared to those treated with nilotinib alone. Final updated results will be presented.




Conclusion cited from the abstract: We present a gene expression model that distinguishes patients who achieved a DMR from those with a poor response to treatment at 5 years. The approach for sample selection optimized the chances of finding a biological and clinical signal and may be applicable to all CML patients initiating TKI therapy. This work could yield new therapeutic targets that could potentially turn a patient biologically determined to be a poor responder into a good responder who might even achieve a TFR.




Conclusion cited from the abstract: High-risk ACA herald death by BC already at low blast levels and may help to define CML end phase in a subgroup of patients at an earlier time than is possible with current blast thresholds. Cytogenetic monitoring is indicated when signs of progression surface and response to therapy is unsatisfactory. More intensive therapy may be indicated at emergence of high-risk ACA.