TY - JOUR
T1 - Venetoclax and hypomethylating agents in acute myeloid leukemia
T2 - Mayo Clinic series on 86 patients
AU - Morsia, Erika
AU - McCullough, Kristen
AU - Joshi, Maansi
AU - Cook, Joselle
AU - Alkhateeb, Hassan B.
AU - Al-Kali, Aref
AU - Begna, Kebede
AU - Elliott, Michelle
AU - Hogan, William
AU - Litzow, Mark
AU - Shah, Mithun
AU - Pardanani, Animesh
AU - Patnaik, Mrinal
AU - Tefferi, Ayalew
AU - Gangat, Naseema
N1 - Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2020/12
Y1 - 2020/12
N2 - 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- naïve and relapsed/refractory AML patients. A total of 44 treatment-naïve 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 with TP53, FLT3, NPM1 and IDH mutations (P =.31). Moreover, CEPBA mutations (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, and BCOR mutations predicted complete response. Survival distinctions were based on CR/CRi (median survival 15 vs 3 months with/without CR/CRi; P <.001), and TP53 mutation status (P =.04). In summary, we corroborate existing reports demonstrating superior response and prolonged survival with venetoclax and HMA in treatment -naïve and relapsed/refractory AML patients regardless of genotype. Additionally, we identify unique predictors of response to therapy which require validation.
AB - 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- naïve and relapsed/refractory AML patients. A total of 44 treatment-naïve 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 with TP53, FLT3, NPM1 and IDH mutations (P =.31). Moreover, CEPBA mutations (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, and BCOR mutations predicted complete response. Survival distinctions were based on CR/CRi (median survival 15 vs 3 months with/without CR/CRi; P <.001), and TP53 mutation status (P =.04). In summary, we corroborate existing reports demonstrating superior response and prolonged survival with venetoclax and HMA in treatment -naïve and relapsed/refractory AML patients regardless of genotype. Additionally, we identify unique predictors of response to therapy which require validation.
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U2 - 10.1002/ajh.25978
DO - 10.1002/ajh.25978
M3 - Article
C2 - 32833294
AN - SCOPUS:85090980268
SN - 0361-8609
VL - 95
SP - 1511
EP - 1521
JO - American journal of hematology
JF - American journal of hematology
IS - 12
ER -