Poor prognosis and limited efficacy of intensive chemotherapy approaches for patients with TP53-mutated myeloid malignancies were confirmed in study results published in Leukemia & Lymphoma.

Jan Philipp Bewersdorf, MD, of the department of internal medicine, section of hematology at the Yale School of Medicine in New Haven, Connecticut, and colleagues conducted the single-center retrospective cohort study from September 1, 2015, to May 31, 2019 (follow-up ended on July 4, 2019). The aims of the study were to describe the clinical, cytogenetic, and molecular characteristics of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with TP53 mutations and to analyze patient responses and outcomes with different treatment modalities.

Of the 83 participants in the study, the majority were Caucasian (88%); 51.8% were women and the median age was 69 years. Most patients had complex karyotypes (90%), and nearly 40% of patients developed therapy-related malignancies.

Frontline treatment included intensive chemotherapy (24.1%), low-intensity treatment (42.2%), best supportive care or hydroxyurea only (22.9%), targeted therapy (3.6%), or other treatments (8.4%). 


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The median follow up was 6.4 months. The median overall survival (OS) and 1-year OS rate were 7.6 months and 22.6%, respectively. Among patients with AML, the median OS was 6.7 months and 1-year OS rate was 16%. Among patients with MDS, the median OS was 10 months and the 1-year OS rate was 31.1%.

For patients with AML, intensive chemotherapy did not improve median OS compared with low-intensity treatment (8.8 months vs 9.4 months, respectively; hazard ratio [HR], 0.63). The 1-year OS rates for intensive chemotherapy and low-intensity therapy were 25.0% and 14.3%, respectively (P =.46); complete response rates were 45.0% and 14.3%, respectively.

Among participents with MDS, no patients received induction chemotherapy as frontline treatment. For the 19 patients with MDS who received hypomethylating agent-based therapies, the median OS was 12.1 months. For patients who received hydroxyurea or best supportive care only, the median OS was 0.8 months.

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Notably, the 11 patients who underwent allogeneic hematopoietic stem cell transplant (alloHSCT) had a significantly longer median OS than those who did not (HR, 0.08; P =.002). Therefore, the authors suggested the alloHSCT should be considered for eligible patients with TP53-mutated myeloid neoplasms.

Limitations of the study included the retrospective design, small sample size, and short follow-up durations.

“In conclusion, our data confirm the limited efficacy of intensive chemotherapy approaches for TP53-mutated patients with myeloid neoplasms and suggest that a minority of patients achieve long-term survival with alloHSCT,” wrote the authors.

Reference

Bewersdorf JP, Shallis RM, Gowda L, et al. Clinical outcomes and characteristics of patients with TP53-mutated acute myeloid leukemia or myelodysplastic syndromes: a single center experience [published online May 2, 2020]. Leuk Lymphoma. doi: 10.1080/10428194.2020.1759051

This article originally appeared on Hematology Advisor