67 year old male with hx of CML since 2005. He progressed on multiple medications as follows: progressed on gleevec, tasignia; was intolerant to sprycel that was stopped due to severe pleural effusion and edema. Based on kinase mutation profile received bosutinib for about one year before progression. Currently he's on asciminib since early 2023. Initially has reduction of BCR/ABL from 10% to nadir of 2% and now increasing to 11%. He continues to have hematological response. Bone marrow biopsy is pending. How would you approach this condition? Would you consider ponatinib or a trial of dasatinib with close monitoring since he did not progress on it?
In this case where pt is resistant to multiple TKI, I would first make sure that he is being compliant with the medication and/or not taking any additional medications that are interfering with absorption of the TKI (i.e. PPI or H2 blockers). If that isn't an issue, I would base treatment on kinase domain mutation; however, my general feel is that this patient will need ponatinib and/or allogeneic stem cell transplant. Checking a myeloid NGS panel to assess for additional somatic mutations may provide some guidance as well.
