Abstract
Mutations in the tumor suppressor gene TP53 are detected in 5–10% of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes. TP53 mutations have been associated with complex karyotypes, therapy-related malignancies, lower response rates to cytotoxic chemotherapy, and an overall adverse prognosis. In this single-center retrospective study, we analyzed the clinicopathologic characteristics and outcomes of 83 patients with TP53-mutated myeloid malignancies treated at Yale Cancer Center between 9/2015 and 5/2019. Complex karyotypes (n = 75; 90%) and therapy-related malignancies (n = 32; 39%) were common. Median overall survival (OS) was 7.6 months. Intensive chemotherapy did not improve OS compared to lower-intensity treatment for AML patients. Patients who underwent allogeneic hematopoietic stem cell transplant (alloHSCT) had a significantly longer median OS, despite relatively limited follow-up. 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.
Disclosure statement
S.D.G. has consulted for and receives research funding from Celgene; personal fees from Abbvie, Jazz Pharmaceuticals, Kyowa Hakko Kirin, Tolero Pharmaceuticals, and Daiichi Sankyo outside of submitted work. N.A.P. consulted for and received honoraria from Alexion, Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, Celgene, Bristol-Myers Squib and CTI biopharma. N.A.P. received research funding (all to the institution) from Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Sunesis Pharmaceuticals, Jazz Pharmaceuticals, Pfizer, Astex Pharmaceuticals, CTI biopharma, Celgene, Genentech, AI Therapeutics, Samus Therapeutics, Arog Pharmaceuticals and Kartos Therapeutics. A.M.Z. received research funding (institutional) from Celgene, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, Novartis, Aprea, and ADC Therapeutics. A.M.Z had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Trovagene, Takeda, Ionis, and Epizyme. A.M.Z received travel support for meetings from Pfizer, Novartis, and Trovagene. None of these relationships were related to the development of this manuscript. The other authors have no relevant conflicts of interest to declare.