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Association details:
| Biomarker: | ASXL1 mutation |
|---|---|
| Cancer: | Myelodysplastic Syndrome |
| Drug: | Venclexta (venetoclax) (Bcl2 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)
Excerpt:
...- AML with any adverse cytogenetics, TP53 mutation, RUNX1 mutation, ASXL1, 11q23/KMT2 rearrangements...
Trial ID:
Source:
Title:
Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN
Excerpt:
...- a history of mutation in TP53, RUNX1, or ASXL1...
Trial ID:
Less C2 evidence
Source:
Title:
Assessing the Role of Venetoclax in Combination with Hypomethylating Agents in Higher Risk Myelodysplastic Syndromes
Published date:
12/24/2021
Excerpt:
The overall response rate (ORR) (HI+) was 77% for 1L HMA/Ven compared to 40% 1L HMA (p<.005). The CR/marrow CR (mCR)/PR/HI were 34%/37%/3%/3% compared to 13%/11%/1%/15% for 1L HMA/Ven and IL HMA alone respectively, p <.005. Among pts with ASXL-1 SM, The ORR was 87% (CR 44%) and 32% (CR 8%) for IL HMA/Ven and 1 L HMA alone respectively, p < .005. Among pts with TP53 SM the ORR was 75% and 44% for IL HMA/Ven and 1 L HMA alone respectively, p = .038, however CR rates were 25% versus 17%, p = .47.Among higher risk MDS patients, 1L HMA/Ven combination yields significantly higher complete response rates including ASXL-1 mutant MDS compared to 1L HMA alone.
DOI:
https://doi.org/10.1182/blood-2021-146634
Source:
Title:
Assessing the Role of Venetoclax in Combination with Hypomethylating Agents in Higher Risk Myelodysplastic Syndromes
Published date:
11/04/2021
Excerpt:
We compared outcomes of those pts who received single agent IL HMA, 1L HMA/Ven combination and HMA with Ven add back strategy after HMA failure (R/R MDS HMA/Ven). Focusing on first line therapy, 1127 received 1L HMA alone with no subsequent Ven add back and 35 pts 1L HMA/Ven. Among pts with ASXL-1 SM, The ORR was 87% (CR 44%) and 32% (CR 8%) for IL HMA/Ven and 1 L HMA alone respectively, p < .005. Among pts with TP53 SM the ORR was 75% and 44% for IL HMA/Ven and 1 L HMA alone respectively, p = .038, however CR rates were 25% versus 17%, p = .47. Among higher risk MDS patients, 1L HMA/Ven combination yields significantly higher complete response rates including ASXL-1 mutant MDS compared to 1L HMA alone.
Secondary therapy:
Hypomethylating agent
DOI:
10.1182/blood-2021-146634
Source:
Title:
Selective inhibition of BCL-2 is a promising target in patients with high-risk myelodysplastic syndromes and adverse mutational profile
Excerpt:
...ABT-199 treatment in MDS, high-risk MDS patient samples specifically underwent cell death in response to ABT-199 even when harbouring mutations in ASXL1, RUNX1, TP53 or EZH2. ABT-199 effectively targeted the stem- and progenitor compartment in advanced MDS harbouring mutations in ASXL1, RUNX1, TP53 or EZH2 and even proved effective in patients harbouring more than one of the defined high-risk mutations.
DOI:
https://dx.doi.org/10.18632%2Foncotarget.24775
Source:
Title:
ASXL1 mutations are associated with distinct epigenomic alterations that lead to sensitivity to venetoclax and azacytidine
Published date:
09/21/2021
Excerpt:
Upon treatment with VEN, mutant cells demonstrated increased growth inhibition. In addition, genome-wide methylome analysis of primary MDS samples and isogenic cell lines demonstrated increased gene-body methylation in ASXL1 mutant cells, with consequently increased sensitivity to AZA.
DOI:
10.1038/s41408-021-00541-0
