Key Takeaways
Challenging Cases in Cancer
Acute Myeloid Leukemia (AML)
Case Presentation: Newly Diagnosed AML Patient
- A 76-year-old male with CAD, HTN, and hyperlipidemia presented with fatigue and shortness of breath.
- Initial lab results: Pancytopenia, 10% circulating blasts, normal renal and liver function,
normal EKG - Bone marrow biopsy revealed 40% myeloblasts
Initial Workup and Management
- Additional tests and supportive management are needed
- Treatment decisions pending cytogenetics, FISH, and NGS results
Cytogenetics and NGS Results
- Trisomy 8, TET-2 mutation (VAF 30%), IDH1 mutation (VAF 10%)
First-Line Treatment Decisions
- Treatment started with azacitidine and venetoclax with prophylactic antibiotics
- After cycle 1, bone marrow was hypocellular with no increased blasts; cycle 2 was delayed
- for count recovery
- Venetoclax dose was reduced to 14 days on/14 days off
NCCN Recommendations for Lower-Intensity Therapy
- Azacitidine + venetoclax
- Decitabine + venetoclax
- LDAC + venetoclax
- Specific treatments for IDH1, IDH2, CD33, and FLT3 mutations
Relapsed/Refractory Management
- After 13 cycles, counts did not recover, leading to further delay and transfusional support
- Bone marrow biopsy confirmed relapsed AML with 15% myeloblasts
- Cytogenetics showed Trisomy 8; NGS revealed increased TET-2 and IDH1 mutation
- Treatment options in relapsed/refractory setting include clinical trials, less aggressive therapies (HMAs, LDAC, venetoclax), and targeted therapies for IDH1 mutations such as olutasidenib and ivosidenib.
Relapse Assessment and Management post Venetoclax Failure
- Patient started treatment with Olutasidenib (OLU), an IDH1 inhibitor
- OLU was chosen based on real-world data showing superior outcomes compared to ivosidenib (IVO) in IDH1-mutated relapsed/refractory AML after venetoclax failure.
- OLU showed higher CRc, TI, and longer mOS (16.23 vs 2.96 months)
- Further research is needed to validate these findings.