A systematic review of venetoclax for the treatment of unfit AML patients in real-world: is all that glitters gold?
Antonio Solana-AltabellaRebeca Rodriguez-VeigaDavid Martínez-CuadrónPau MontesinosPublished in: Annals of hematology (2024)
Acute myeloid leukemia (AML) is an aggressive hematological disease that mainly affects elderly patients. Following the randomized VIALE-A trial, current standard treatment in patients who are not candidates for intensive chemotherapy consists of the combination of venetoclax (VEN), a selective inhibitor of the anti-apoptotic protein BCL-2, with azacitidine (AZA) or decitabine (DEC). We performed a systematic review to critically assess the growing existing evidence regarding the effectiveness of the VEN-based combinations in unfit adult patients with newly diagnosed AML in the real-world setting. Following PRISMA guidelines, a systematic search of published manuscripts and conference abstracts (European Hematology Association and American Society of Hematology) was conducted (updated March 2024). Primary outcomes were composite complete remission (CRc) and median overall survival (mOS). A total of 73 studies fulfilled inclusion criteria, with a median age of 73 years old. The weighted mean mOS was 10.3 months among 7 138 patients, significantly lower than expected according to the VIALE-A trial (14.7 months), while the weighted mean CRc rate was 58.2% among 5 831 patients, slightly lower to that reported in the VIALE-A (66.4%). Early death rates at 30 and 60 days were 5% and 13%, respectively. The weighted mean percentage of subsequent allogeneic transplant was 15.4%. In conclusion, breakthrough mOS reported in the VIALE-A trial using VEN-AZA was not well reproduced in real world for unfit newly diagnosed AML patients, while CRc rates were more consistent. Strategies to optimize patient selection, dosing regimens, and supportive care are crucial to improve outcomes in real-world.
Keyphrases
- acute myeloid leukemia
- newly diagnosed
- phase iii
- ejection fraction
- end stage renal disease
- allogeneic hematopoietic stem cell transplantation
- study protocol
- phase ii
- clinical trial
- magnetic resonance
- randomized controlled trial
- healthcare
- open label
- room temperature
- systematic review
- prognostic factors
- quantum dots
- cell death
- squamous cell carcinoma
- rheumatoid arthritis
- bone marrow
- palliative care
- metabolic syndrome
- stem cell transplantation
- double blind
- patient reported outcomes
- pain management
- case report
- highly efficient
- placebo controlled
- ionic liquid
- magnetic resonance imaging
- type diabetes
- health insurance
- binding protein
- adipose tissue
- free survival
- reduced graphene oxide
- computed tomography
- hematopoietic stem cell
- smoking cessation