Premium
Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL‐2 and/or BIM
Author(s) -
Huemer Florian,
Melchardt Thomas,
Jansko Bettina,
Wahida Adam,
Jilg Stefanie,
Jost Philipp J.,
Klieser Eckhard,
Steiger Katja,
Magnes Teresa,
Pleyer Lisa,
GreilRessler Sigrun,
Rass Christof,
Greil Richard,
Egle Alexander
Publication year - 2019
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13218
Subject(s) - venetoclax , medicine , hypomethylating agent , oncology , refractory (planetary science) , myeloid leukemia , chemotherapy , population , leukemia , gastroenterology , chronic lymphocytic leukemia , biology , biochemistry , gene expression , environmental health , astrobiology , dna methylation , gene
Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL‐2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL‐2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non‐responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.