TY - JOUR
T1 - Outcomes of TP53-mutant acute myeloid leukemia with decitabine and venetoclax
AU - Kim, Kunhwa
AU - Maiti, Abhishek
AU - Loghavi, Sanam
AU - Pourebrahim, Rasoul
AU - Kadia, Tapan M.
AU - Rausch, Caitlin R.
AU - Furudate, Ken
AU - Daver, Naval G.
AU - Alvarado, Yesid
AU - Ohanian, Maro
AU - Sasaki, Koji
AU - Short, Nicholas J.
AU - Takahashi, Koichi
AU - Yilmaz, Musa
AU - Tang, Guilin
AU - Ravandi, Farhad
AU - Kantarjian, Hagop M.
AU - DiNardo, Courtney D.
AU - Konopleva, Marina Y.
N1 - Publisher Copyright:
© 2021 American Cancer Society
PY - 2021/10/15
Y1 - 2021/10/15
N2 - Background: TP53 mutation (TP53mut) confers an adverse prognosis in acute myeloid leukemia (AML). Venetoclax with hypomethylating agents is a current standard for older patients; however, recent reports suggest that TP53mut confers resistance to venetoclax. The authors investigated the outcomes of patients with TP53mut AML who were treated with a 10-day decitabine and venetoclax (DEC10-VEN) (ClinicalTrials.gov identifier NCT03404193). Methods: Patients with newly diagnosed AML received decitabine 20 mg/m2 for 10 days every 4 to 6 weeks for induction, followed by decitabine for 5 days after response. The venetoclax dose was 400 mg daily. TP53mut was identified in bone marrow samples using next-generation sequencing, with sensitivity of 5%. Outcomes were analyzed according to European LeukemiaNet 2017 guidelines. Results: Among 118 patients (median age, 72 years; age range, 49-89 years), 63 (53%) had secondary AML, 39 (33%) had AML with complex karyotype, and 35 (30%) had TP53mut AML. The median TP53 variant allele frequency was 32% (interquartile range, 16%-65%), 8 patients (23%) had only a single TP53 mutation, 15 (43%) had multiple mutations, and 12 (34%) had mutation and deletion. Outcomes were significantly worse in patients who had TP53mut AML compared with those who had wild-type TP53 AML, with an overall response rate of 66% vs 89% (P =.002), a complete response/complete response with incomplete hematologic recovery rate of 57% vs 77% (P =.029), and a 60-day mortality of 26% vs 4% (P <.001), respectively. Patients with TP53mut versus wild-type TP53 had shorter overall survival at 5.2 versus 19.4 months, respectively (hazard ratio, 4.67; 95% CI, 2.44-8.93; P <.0001), and shorter relapse-free survival at 3.4 versus 18.9 months (hazard ratio, 4.80; 95% CI, 1.97-11.69; P <.0001), respectively. Outcomes with DEC10-VEN in patients with TP53mut AML were comparable to historical results with 10-day decitabine alone. Conclusions: Patients with TP53mut AML have lower response rates and shorter survival with DEC10-VEN.
AB - Background: TP53 mutation (TP53mut) confers an adverse prognosis in acute myeloid leukemia (AML). Venetoclax with hypomethylating agents is a current standard for older patients; however, recent reports suggest that TP53mut confers resistance to venetoclax. The authors investigated the outcomes of patients with TP53mut AML who were treated with a 10-day decitabine and venetoclax (DEC10-VEN) (ClinicalTrials.gov identifier NCT03404193). Methods: Patients with newly diagnosed AML received decitabine 20 mg/m2 for 10 days every 4 to 6 weeks for induction, followed by decitabine for 5 days after response. The venetoclax dose was 400 mg daily. TP53mut was identified in bone marrow samples using next-generation sequencing, with sensitivity of 5%. Outcomes were analyzed according to European LeukemiaNet 2017 guidelines. Results: Among 118 patients (median age, 72 years; age range, 49-89 years), 63 (53%) had secondary AML, 39 (33%) had AML with complex karyotype, and 35 (30%) had TP53mut AML. The median TP53 variant allele frequency was 32% (interquartile range, 16%-65%), 8 patients (23%) had only a single TP53 mutation, 15 (43%) had multiple mutations, and 12 (34%) had mutation and deletion. Outcomes were significantly worse in patients who had TP53mut AML compared with those who had wild-type TP53 AML, with an overall response rate of 66% vs 89% (P =.002), a complete response/complete response with incomplete hematologic recovery rate of 57% vs 77% (P =.029), and a 60-day mortality of 26% vs 4% (P <.001), respectively. Patients with TP53mut versus wild-type TP53 had shorter overall survival at 5.2 versus 19.4 months, respectively (hazard ratio, 4.67; 95% CI, 2.44-8.93; P <.0001), and shorter relapse-free survival at 3.4 versus 18.9 months (hazard ratio, 4.80; 95% CI, 1.97-11.69; P <.0001), respectively. Outcomes with DEC10-VEN in patients with TP53mut AML were comparable to historical results with 10-day decitabine alone. Conclusions: Patients with TP53mut AML have lower response rates and shorter survival with DEC10-VEN.
KW - TP53
KW - acute myeloid leukemia (AML)
KW - decitabine
KW - outcome
KW - venetoclax
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U2 - 10.1002/cncr.33689
DO - 10.1002/cncr.33689
M3 - Article
C2 - 34255353
AN - SCOPUS:85109797410
SN - 0008-543X
VL - 127
SP - 3772
EP - 3781
JO - Cancer
JF - Cancer
IS - 20
ER -