Question: Is there anecdotal evidence (or data) to support that lower doses of asciminib for patients with T315I mutations in CP CML with CCyR or better maintain or deepen response? What doses have been used?
Case: The patient is a 58 year old physically fit female with T2DM and variant transcript CP CML (undetectable by QPCR). No response to dasatinib and T315I detected.
On ponatinib predominantly dosed at 30 mg daily (thrombocytopenia) FISH declined from 28% to 1.4% over 4 months. After 5 months of therapy she developed acute appendicitis and underwent appendectomy. Ponatinib was stopped immediately. The patient was readmitted for small bowel obstruction and abscesses. This was initially managed conservatively with a percutaneous drain, but there was no resolution of ongoing bowel obstruction and she underwent exploratory laparotomy and ileocecectomy. Final pathology diagnosis from the last surgery revealed a portion of the ileum and colon with acute serositis, subserosal hemorrhage and fibrosis, and minimal mucosal inflammation. No perforation was identified. Because of wound healing issues associated with ponatinib use, ponatinib continued to be held. The patient made a good recovery.
Asciminib was started 7 weeks after stopping ponatinib at 200 mg BID. Response continued to deepen and the patient achieved CCyR by FISH on asciminib. She tolerates asciminib very well and has an excellent quality of life. Her only complaint was intermittent abdominal pain, possibly associated with eating. LFTs and lipase all within normal limits on monitoring. Eight months after starting asciminib therapy, she presented with transaminitis (ALT 1640 and AST 1880), elevated total bilirubin at 1.8 (predominantly direct) and abdominal pain. Lipase was within normal limits and there was no evidence of pancreatitis. Cholelithiasis was seen by abdominal US and CT of the abdomen/pelvis, but no cholecystitis was evident. By US no biliary duct dilatation was seen and it is unclear if gallstones contributed to episode. There were no other CT findings. The pain has resolved and transaminitis is normalizing off therapy. The plan is to restart asciminib at a reduced dose of 80-120 mg BID with very careful follow-up.