^
Association details:
| Biomarker: | TP53 mutation |
|---|---|
| Cancer: | Myelodysplastic Syndrome |
| Drug: | Venclexta (venetoclax) (Bcl2 inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Study on the Safety and Efficacy of Elderly High-risk MDS/AML Patients Undergoing Hematopoietic Stem Cell Transplantation with Venetoclax Combined with Dicitabine-based Preconditioning Regimen
Excerpt:
...1.Primary hematologic disease was high-risk myelodysplastic syndrome or acute myeloid leukemia, with allogeneic HSCT indications; 2.High-risk MDS/AML includes the following conditions: (1)Compliance with the 2017 WHO classification MDS diagnostic criteria and has one of the following features: 1)Compliance with MDS-EB2 diagnosis; 2)With poor prognosis chromosomal karyotype; 3)IPSS-R score is extremely high risk; 4)Positive TP53 mutation in the first diagnosis. ...
Trial ID:
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:
More C2 evidence
Source:
Title:
Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS
Excerpt:
...Mutated P53 or Ras pathway genes (CBL, NRAS, KRAS, NF1, PTPN1) or DNMT 3a or ASXL1 or RUNX1 3....
Trial ID:
Source:
Title:
Venetoclax Added to Fludarabine + Busulfan Prior to Transplant and to Maintenance Therapy for AML, MDS, and MDS/MPN
Excerpt:
...- Presence of a mutation in TP53...
Trial ID:
Source:
Title:
Venetoclax and Decitabine in Treating Participants With Relapsed/Refractory Acute Myeloid Leukemia or Relapsed High-Risk Myelodysplastic Syndrome
Excerpt:
...- Patients with newly diagnosed AML with poor risk complex karyotype and/or TP53 deletions/mutations equal or younger than 60 year old...
Trial ID:
Source:
Title:
Venetoclax and Decitabin Based Conditioning Regimen Followed With Post-HSCT Decitabin Maintenance Therapy in TP53 Mutant AML/MDS Patients
Excerpt:
...AML or MDS diagnosed according to 2016 WHO criteria with TP53 mutation before enrollment; 2....
Trial ID:
Less C2 evidence
Source:
Title:
Low-Dose Weekly Decitabine and Venetoclax in TP53-Mutated Myeloid Malignancies
Published date:
09/21/2022
Excerpt:
We conducted a retrospective analysis of patients with TP53mut MDS/AML at our institution treated with 400 mg Ven...Overall response rate was 100%: 5/5 front-line patients had complete remissions (CR), and the R/R patient achieved a morphologic leukemia-free state....Weekly Ven with low-dose subQ Dec is well tolerated, yielding high response rates in TP53mut MDS/AML.
Secondary therapy:
decitabine
Source:
Title:
A Phase I/II Study of Venetoclax in Combination With ASTX727 (Decitabine/Cedazuridine) in Treatment-Naïve High-Risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
Published date:
09/21/2022
Excerpt:
The ORR was 95% with 3 pts achieving CR (16%) and 15 pts achieving marrow CR (79%). All pts achieved a response within 1 cycle among which 7 pts, including one with TP53mut, proceeded to hematopoietic stem cell transplant...Ven+ASTX727 combination appears safe and demonstrates preliminary efficacy in pts with higher risk MDS or CMML with excess blasts. Total-oral regimen of Ven+ASTX727 combination appears to be a promising strategy for high-risk MDS or CMML pts.
Secondary therapy:
decitabine/cedazuridine
Trial ID:
Source:
Title:
Molecular stratification of response and survival of venetoclax in combination with hypomethylating agents in AML.
Published date:
05/26/2022
Excerpt:
We retrospectively analyzed 41 patients with AML treated with upfront venetoclax + HMAs from July 2017 to December 2020 at VCU Massey Cancer Center….Nine patients had TP53mut with a CRR of 33.3% and OS 12.6 months….Survival with venetoclax + HMA appears to numerically favor TP53mut AML when compared to more intensive strategies, consistent with prior literature reporting favorable responses to HMA monotherapy in this subset of disease.
Secondary therapy:
decitabine
DOI:
10.1200/JCO.2022.40.16_suppl.e19033
Source:
Title:
Results of a phase 1 trial of azacitidine with venetoclax in relapsed/refractory higher-risk myelodysplastic syndrome (MDS).
Published date:
05/26/2022
Excerpt:
CONTRADICTING EVIDENCE: This is a phase 1 study evaluating patients ≥ 18 years old after HMA failure with adequate organ function and performance status were enrolled....All patients received Aza 75mg/m2 IV/SC on D1-5. A 3+3 Ven dose escalation was utilized...Four patients had no response with 3 of those having TP53 mutations….TP53 mutations and complex karyotypes still confer poor prognosis despite the addition of Venetoclax.
DOI:
10.1200/JCO.2022.40.16_suppl.e19068
Trial ID:
Source:
Title:
A PHASE I/II STUDY OF VENETOCLAX IN COMBINATION WITH ASTX727 (DECITABINE/CEDAZURIDINE) IN TREATMENT‐NAÏVE HIGH‐RISK MYELODYSPLASTIC SYNDROME (MDS) OR CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)
Published date:
05/12/2022
Excerpt:
All pts achieved a response within 1 cycle among which 4 pts, including one with TP53mut...Ven+ASTX727 combination appears safe and demonstrates preliminary efficacy in pts with higher risk MDS or CMML...
Secondary therapy:
decitabine/cedazuridine
Trial ID:
Source:
Title:
Low-Dose Weekly Decitabine and Venetoclax in TP53-Mutated Myeloid Malignancies
Published date:
11/04/2021
Excerpt:
The overall response rate (ORR) was 100%: 4/4 frontline pts had complete remissions (CR), and the 1 R/R pt achieved morphologic leukemia-free state (MLFS). Median time to best response was 2.9 mo….Combination weekly Ven with subcutaneous low-dose Dec is well tolerated yielding high rates of clinical and molecular response in pts with TP53mut MDS/AML.
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
