Poorprognosis and limited efficacy of intensive chemotherapy approaches forpatients with TP53-mutated myeloidmalignancies 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.

Ofthe 83 participants in the study, the majority were Caucasian (88%); 51.8% werewomen 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%).

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

Forpatients with AML, intensive chemotherapy did not improve median OS compared withlow-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-intensitytherapy were 25.0% and 14.3%, respectively (P =.46); complete response rates were 45.0% and 14.3%, respectively.

Amongparticipents with MDS, no patients received induction chemotherapy as frontlinetreatment. For the 19 patients with MDS who received hypomethylating agent-basedtherapies, the median OS was 12.1 months. For patients who received hydroxyureaor best supportive care only, the median OS was 0.8 months.

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 eligiblepatients with TP53-mutated myeloidneoplasms.

Limitationsof the study included the retrospective design, small sample size, and shortfollow-up durations.

Inconclusion, our data confirm the limited efficacy of intensive chemotherapyapproaches for TP53-mutated patientswith myeloid neoplasms and suggest that a minority of patients achievelong-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

Read more from the original source:
Novel Therapies Needed: Poor Prognosis of Patients With TP53-Mutated Myeloid Malignancies - Cancer Therapy Advisor