Venetoclax and hypomethylating agent (HMA) combination therapy is FDA-approved for elderly or unfit acute myeloid leukemia (AML) patients unable to withstand intensive chemotherapy. The primary objective of the current study was to impart our institutional experience with the above regimen, outlining response, survival outcomes, and its determinants amongst 86 treatment- naive and relapsed/refractory AML patients. A total of 44 treatment-naive AML patients, median age 73.5 years, enriched with secondary, therapy related and ELN adverse risk disease (n = 27) were studied. The CR/CRi rates of 50% (22 of 44 patients) were superior to 23% in a matched AML cohort treated with HMA alone (P= .005). Response rates were similar withTP53,FLT3,NPM1andIDHmutations (P= .31). Moreover,CEPBAmutations (P= .03) and neutropenia (P= .05) emerged as predictors of complete response. Survivalwas prolonged in patients achieving CR/CRi (17 vs 3 months without CR/CRi,P < .001; conversely adverse ELN risk portended inferior survival. Amongst 42 relapsed/refractory AML patients, half received >= 2 prior therapies excluding transplant, and 15 (35.7%) had received HMA. A group of 14 patients (33.3%) attained CR/CRi; age > 65 years, AML with myelodysplasia,JAK2,DNMT3A, andBCORmutations predicted complete response. Survival distinctions were based on CR/CRi (median survival 15 vs 3 months with/without CR/CRi;P < .001), andTP53mutation status (P= .04). In summary, we corroborate existing reports demonstrating superior response and prolonged survival with venetoclax and HMA in treatment -naive and relapsed/refractory AML patients regardless of genotype. Additionally, we identify unique predictors of response to therapy which require validation.

Venetoclax and hypomethylating agents in acute myeloid leukemia: Mayo Clinic series on 86 patients / Morsia, Erika; Mccullough, Kristen; Joshi, Maansi; Cook, Joselle; Alkhateeb, Hassan B; Al-Kali, Aref; Begna, Kebede; Elliott, Michelle; Hogan, William; Litzow, Mark; Shah, Mithun; Pardanani, Animesh; Patnaik, Mrinal; Tefferi, Ayalew; Gangat, Naseema. - In: AMERICAN JOURNAL OF HEMATOLOGY. - ISSN 1096-8652. - STAMPA. - 95:12(2020), pp. 1511-1521. [10.1002/ajh.25978]

Venetoclax and hypomethylating agents in acute myeloid leukemia: Mayo Clinic series on 86 patients

Morsia, Erika
Primo
;
2020-01-01

Abstract

Venetoclax and hypomethylating agent (HMA) combination therapy is FDA-approved for elderly or unfit acute myeloid leukemia (AML) patients unable to withstand intensive chemotherapy. The primary objective of the current study was to impart our institutional experience with the above regimen, outlining response, survival outcomes, and its determinants amongst 86 treatment- naive and relapsed/refractory AML patients. A total of 44 treatment-naive AML patients, median age 73.5 years, enriched with secondary, therapy related and ELN adverse risk disease (n = 27) were studied. The CR/CRi rates of 50% (22 of 44 patients) were superior to 23% in a matched AML cohort treated with HMA alone (P= .005). Response rates were similar withTP53,FLT3,NPM1andIDHmutations (P= .31). Moreover,CEPBAmutations (P= .03) and neutropenia (P= .05) emerged as predictors of complete response. Survivalwas prolonged in patients achieving CR/CRi (17 vs 3 months without CR/CRi,P < .001; conversely adverse ELN risk portended inferior survival. Amongst 42 relapsed/refractory AML patients, half received >= 2 prior therapies excluding transplant, and 15 (35.7%) had received HMA. A group of 14 patients (33.3%) attained CR/CRi; age > 65 years, AML with myelodysplasia,JAK2,DNMT3A, andBCORmutations predicted complete response. Survival distinctions were based on CR/CRi (median survival 15 vs 3 months with/without CR/CRi;P < .001), andTP53mutation status (P= .04). In summary, we corroborate existing reports demonstrating superior response and prolonged survival with venetoclax and HMA in treatment -naive and relapsed/refractory AML patients regardless of genotype. Additionally, we identify unique predictors of response to therapy which require validation.
2020
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/315658
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 35
  • Scopus 84
  • ???jsp.display-item.citation.isi??? 81
social impact