Asciminib induced Pancreatitis in Chronic Myeloid Leukemia: A Case Report and Literature Review
Introduction/Background/Significance: Asciminib, a BCR-ABL1 tyrosine kinase inhibitor (TKI) that specifically targets the ABL myristoyl pocket, serves as a therapeutic option for patients with chronic myeloid leukemia (CML) who are intolerant to other ATP-competitive TKIs. The most common adverse events associated with Asciminib include fatigue, thrombocytopenia, arthralgia, and anemia, while clinical pancreatitis is less commonly reported [1]. We present a case of acute pancreatitis secondary to Asciminib, leading to temporary discontinuation of the drug.
Materials and Methods/Case Presentation/Objective: A 69-year-old female with a medical history of rheumatoid arthritis, psoriatic arthritis (on Abatacept), and CML presented with abdominal pain and non-bilious vomiting for two days. She had been diagnosed with chronic-phase CML after leukocytosis was detected during routine laboratory work. At diagnosis, BCR-ABL1 was 21.353%, and bone marrow biopsy revealed hypocellular marrow with myeloid hyperplasia and no evidence of excess blasts. Peripheral flow cytometry showed 0.1% myeloblasts. Two weeks prior to presentation, the patient was started on Asciminib 80 mg daily, which was later adjusted to 40 mg twice daily due to side effects including hypertension, headache, and joint pain. On examination, her vital signs were stable, and she had epigastric and bilateral lumbar region tenderness. Laboratory results showed: WBC 17 ×109/L, hemoglobin 13.8 g/dL, platelets 232 ×109/L, lipase 61 U/L, triglycerides 47 mg/dL. A CT scan of the abdomen and pelvis with IV contrast revealed peripancreatic fat stranding and inflammation in the region of the pancreatic head, suggestive of acute pancreatitis. She was treated with intravenous fluids, and Asciminib was held.
Results/Description/Main Outcome Measures: In a retrospective study of 77 patients receiving Asciminib, pancreatitis was observed in two patients, both of whom had prior episodes of pancreatitis [1]. Although the ASCEMBL trial did not report pancreatitis as an adverse event, patients with a history of pancreatitis were excluded [2]. In a clinical trial, pancreatitis occurred in 3% of patients receiving Asciminib at doses greater than 40 mg twice daily[3]. These cases were managed through drug discontinuation or dose modification. Additionally, asymptomatic elevations in lipase or amylase were observed in 35 patients [3]. This case report highlights the importance of recognizing and managing pancreatitis as a dose-limiting adverse event of Asciminib, a drug considered to have superior efficacy, and a favorable safety profile compared to other TKIs.
Conclusions: Asciminib is a promising treatment option for CML patients intolerant to ATP-competitive TKIs. This case report contributes to the existing literature by highlighting the potential for clinical pancreatitis in patients receiving Asciminib, particularly at higher doses, which may necessitate drug discontinuation or dose reduction.
References
1. Pérez-Lamas, L., et al., Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors. Cancers (Basel), 2023. 15(4).
2. Réa, D., et al., A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood, 2021. 138(21): p. 2031-2041.
3. Hughes, T.P., et al., Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure. New England Journal of Medicine, 2019. 381(24): p. 2315-2326.
