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- Title
Patients with TP53 -Mutated Acute Myeloid Leukemia Receiving Intensive Induction Therapy Have Superior Outcomes Due to a Higher Rate of Salvage Therapy: A Single Institution, Retrospective Study.
- Authors
Sumransub, Nuttavut; Steinwand, Gabriel K.; Cordner, Keith; Lee, Yoonkyu; Cao, Qing; Allred, Jeremy; Bachanova, Veronika; Juckett, Mark; Eckfeldt, Craig; Maakaron, Joseph E.; Tracy, Sean I.; Ramesh, Vidhyalakshmi; Nelson, Andrew C.; Yohe, Sophia; Sachs, Zohar
- Abstract
Simple Summary: Mutations in the gene, TP53, define the most treatment-resistant subtype of acute myeloid leukemia (AML). Patients with TP53-mutated AML invariably develop disease recurrence after treatment, leading to short survival times. Previous studies have shown that less than 10% of these patients survive beyond 2 years after diagnosis. Moreover, the best treatment approach for these patients is still unclear. Our study is the first to analyze therapy results beyond first-line treatment, highlighting the importance of therapy sequencing in managing these patients. We found that sequential treatment with intensive chemotherapy followed by a less-intensive regimen achieved the highest remission rate of over 65%. Eligible patients should then receive blood stem cell transplantation from a donor, which significantly improves long-term survival. Our study provides crucial data to guide management and optimize therapy sequencing for better survival in this treatment-resistant disease. Background: TP53 mutations (TP53m) define the most treatment-refractory acute myeloid leukemia (AML) subtype. Optimal treatment approaches have not been established in this setting. We reviewed our institutional experience to identify therapy sequencing, treatment response, and survival patterns in these patients. Methods: This study was a single-center, retrospective cohort analysis. Results: Our cohort includes 86 TP53m and 337 TP53 wild-type (TP53wt) adult AML patients. TP53m AML patients presented with lower bone marrow and peripheral blasts; none presented with hyperleukocytosis. Patients who received intensive treatment up front demonstrated superior overall survival (OS) over those receiving first-line non-intensive therapy (2-year OS 22% versus 7%; p = 0.02). However, the complete remission (CR) rates among the first-line intensive and non-intensive therapy groups were comparable (21.9% and 29.4%, respectively, p = 0.49). The improved OS is therefore attributed to superior cumulative CR in the intensive group. First-line intensively treated patients were more likely to receive and respond to salvage, leading to a cumulative CR rate of 65.7% (versus 29.4%, p = 0.003). Achieving CR at any point is strongly associated with superior survival outcomes with 2-year OS of 31% versus 0% for those not achieving CR ever (p < 0.01). Conclusions: We find that TP53m AML rarely presents with oncological emergencies, suggesting that clinical trial enrollment is feasible in this group. Additionally, in our cohort, intensive induction therapies lead to superior survival outcomes attributed to successful salvage therapy. These data suggest that strategic therapy sequencing and salvage therapy may be important in optimizing outcomes for TP53m AML patients.
- Subjects
THERAPEUTIC use of antineoplastic agents; RESEARCH funding; SALVAGE therapy; PATHOLOGIC complete response; TREATMENT effectiveness; RETROSPECTIVE studies; CANCER patients; DISEASE remission; DESCRIPTIVE statistics; TUMOR suppressor genes; ONCOGENES; MEDICAL records; ACQUISITION of data; GENETIC mutation; INDUCTION chemotherapy; OVERALL survival; EVALUATION
- Publication
Cancers, 2024, Vol 16, Issue 16, p2784
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16162784