|The following article features coverage from the 2021 American Society of Hematology Annual Meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Allogeneic hematopoietic stem cell transplant (allo-HSCT) is associated with superior survival in patients with TP53-mutated acute myeloid leukemia (AML), but rates of allo-HSCT fell substantially in 2020-2021, according to research presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
“TP53 mutations occur in 10% to 20% of patients with AML. It confers poor prognosis and a chemo-refractory phenotype,” said study presenter Talha Badar, MD, of the Mayo Clinic in Jacksonville, Florida.
“With the advent of venetoclax-based combinations and CPX-351, a certain subset of patients improved. However, the optimal strategy to manage TP53-mutated AML patients remains unclear and to be explored,” he added.
With this in mind, Dr Badar and colleagues conducted a retrospective analysis of 315 patients with TP53-mutated AML. The patients were treated at 9 academic centers across the United States between 2012 and 2021.
The patients were stratified into 4 groups based on the progressive use of novel agents in clinical trials and their approvals as AML induction therapy during various time periods:
- Group 1, 2012-2017 (n=74)
- Group 2, 2018-2019 (n=121)
- Group 3, 2019-2020 (n=72)
- Group 4, 2020-2021 (n=48).
Baseline characteristics were similar across the groups. Overall, the median age was 66 years (range, 18-97 years). The TP53 variant allele fraction was 43%, and 61.5% of patients had co-mutations. The most common co-occurring mutations were DNMT3A (10%), TET2 (9.9%), and ASXL1 (6%).
Patients received the following treatments as induction:
- Hypomethylating agents plus venetoclax — 1.4% of group 1, 21.5% of group 2, 47.2% of group 3, and 54.2% of group 4 (P <.0001)
- 7+3 chemotherapy — 28.4%, 12.4%, 11.1%, and 6.2%, respectively (P =.003)
- CPX-351 — 13.5%, 33.9%, 22.2%, and 6.2%, respectively (P <.001)
- High-dose cytarabine-based treatment — 10.8%, 6.6%, 4.2%, and 4.2%, respectively (P =.39).
The rate of complete response (CR) or CR with incomplete count recovery was 29% overall. It was not significantly different across the groups — 24.2% in group 1, 33% in group 2, 31% in group 3, and 22.9% in group 4 (P =.52).
There was a significant association between receiving hypomethylating agents plus venetoclax and achieving a CR (odds ratio, 2.25; 95% CI, 1.26-4.01; P =.006). However, there was no significant association for CPX-351 (P =.63), 7+3 (P =.18), or high-dose cytarabine-based treatment (P =.65).
After induction/consolidation, 15% of patients received allo-HSCT — 18% in group 1, 17% in groups 2 and 3, and 2% in group 4.
Dr Badar said “it’s hard to tell” if the substantial decrease in allo-HSCT during 2020-2021 is a result of the COVID-19 pandemic because the researchers did not consider that factor in their analysis, but it’s “worth exploring.”
The 18-month progression-free survival rate was 71.5% in group 1, 47.8% in group 2, 42.7% in group 3, and 77.7% in group 4 (P =.032). The 12-month overall survival (OS) rate was 40.5%, 27.6%, 24.8% and 10.0%, respectively (P =.014).
Allo-HSCT was associated with favorable OS (hazard ratio [HR], 0.30; 95% CI, 0.19-0.47; P <.001).
Complex cytogenetics was associated with poor OS (HR, 2.39; 95% CI, 1.47-3.88; P <.001), as was RAS mutation (HR, 3.98; 95% CI, 2.22-7.14; P <.001).
“This the largest experience of TP53-mutated AML patients analyzed by NGS [next-generation sequencing],” Dr Badar said. “Unfortunately, outcomes remain universally dismal, and allo-HSCT appears to improve … survival outcomes.”
“We need effective therapies to improve outcomes of these patients, bridging them to stem cell transplant or prolonging survival for those who are ineligible for stem cell transplant,” he concluded.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Read more of Cancer Therapy Advisor’s coverage of the ASH 2021 meeting by visiting the conference page.
Badar T, Litzow MR, Shallis RM, et al. Multicenter analysis of treatment and outcomes for patient with TP53 mutated AML in the era of novel therapies; Significant impact of allogeneic stem cell transplantation on survival. Presented at ASH 2021; December 11-14, 2021. Abstract 797.