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Case Reports
. 2019 May;102(5):437-441.
doi: 10.1111/ejh.13218. Epub 2019 Feb 28.

Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL-2 and/or BIM

Florian Huemer  1 , Thomas Melchardt  1 , Bettina Jansko  1 , Adam Wahida  2 , Stefanie Jilg  2 , Philipp J Jost  2 , Eckhard Klieser  3 , Katja Steiger  4 , Teresa Magnes  1 , Lisa Pleyer  1 , Sigrun Greil-Ressler  1 , Christof Rass  1 , Richard Greil  1 , Alexander Egle  1
Affiliations
Case Reports

Durable remissions with venetoclax monotherapy in secondary AML refractory to hypomethylating agents and high expression of BCL-2 and/or BIM

Florian Huemer et al. Eur J Haematol. 2019 May.

Abstract

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.

Keywords: BCL-2; BIM; IDH1; IDH2; MCL-1; azacitidine; hypomethylating agents; myeloproliferative neoplasm; secondary acute myeloid leukemia; venetoclax.

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Conflict of interest statement

Florian Huemer: none; Thomas Melchardt: honoraria (Abbvie); Bettina Jansko: none; Adam Wahida: none; Stefanie Jilg: none; Philipp J. Jost: research grant (Abbvie); Eckhard Klieser: none; Katja Steiger: none; Teresa Magnes: none, Lisa Pleyer: consulting (Celgene), honoraria (Celgene), travel grants (Celgene); Sigrun Greil‐Ressler: none; Christof Rass: none; Richard Greil: honoraria (Celgene), consulting (Celgene, Abbvie), research grant (Celgene), travel grants (Janssen); Alexander Egle: honoraria (Abbvie), consulting (Abbvie, Celgene, Janssen), travel grants (Abbvie).

Figures

Figure 1
Figure 1
Overall Survival of Seven Secondary AML Patients Refractory to Hypomethylating Agents from Venetoclax Initiation (A), Immunohistochemistry for BCL‐2, BIM, and MCL‐1 on Myeloblasts (B), and Overall Survival From Venetoclax Initiation Based on Venetoclax Therapy Response (C). A, The tick marks on the curves represent censored patients. B, BCL‐2, BIM, and MCL‐1 expression on myeloblasts based on pretreatment bone marrow biopsies/aspirates. C, Responders included patient #8623 (CR), #17397 (CR), and #24231 (rapid peripheral blast clearing). The tick marks on the curves represent censored patients
See this image and copyright information in PMC

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