TY - JOUR
T1 - Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies
AU - DiNardo, Courtney D.
AU - Rausch, Caitlin R.
AU - Benton, Christopher
AU - Kadia, Tapan
AU - Jain, Nitin
AU - Pemmaraju, Naveen
AU - Daver, Naval
AU - Covert, Wendy
AU - Marx, Kayleigh R.
AU - Mace, Morgan
AU - Jabbour, Elias
AU - Cortes, Jorge
AU - Garcia-Manero, Guillermo
AU - Ravandi, Farhad
AU - Bhalla, Kapil N.
AU - Kantarjian, Hagop
AU - Konopleva, Marina
N1 - Funding Information:
This work was supported in part by the MD Anderson Cancer Center Support Grant (CCSG) CA016672, the Charif Souki Cancer Research Fund, and the MD Anderson Cancer Center Leukemia SPORE CA100632, and by the generous philanthropic contributions to MD Anderson's MDS/AML Moon Shot Program.
Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2018/3
Y1 - 2018/3
N2 - Introduction: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML), and efficacy in lower intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported. Methods: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed. Results: Forty-three patients with median age 68 (range, 25–83) were treated for AML (91%), MDS (5%), or BPDCN (5%). Most (n = 36, 84%) were ≥ salvage-2 treatment status, including prior hypomethylating agent (HMA) in 77%. In combination with VEN, most patients received HMA therapy (n = 31, 72%); eight (19%) received low-dose cytarabine (LDAC). Patients received a median of 2 treatment cycles (range, 1–4). Objective response was observed in 9 (21%) patients, including 2 complete responses (CR), 3 CRi, and 4 morphologic leukemia-free state (MLFS). Median survival was 3.0 months (range, 0.5–8.0), and estimated 6-month survival was 24%. Responses were observed in five (24%) of 21 patients with intermediate-risk cytogenetics, 3 (27%) of 11 IDH1/2-mutant, and 4 (50%) of 8 RUNX1-mutated patients. Two (20%) of 10 TP53-mutated patients responded; both had concurrent RUNX1 mutations. Of the 3 (15%) responding patients with adverse cytogenetics, all had concurrent RUNX1 mutations. Conclusion: Low-intensity chemotherapy, including HMAs or LDAC, in combination with VEN is a viable salvage option, even in multiply relapsed/refractory patients with AML, MDS, and BPDCN. Notable responses were identified in patients with diploid/intermediate cytogenetics, RUNX1, and/or IDH1/2 mutations.
AB - Introduction: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML), and efficacy in lower intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported. Methods: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed. Results: Forty-three patients with median age 68 (range, 25–83) were treated for AML (91%), MDS (5%), or BPDCN (5%). Most (n = 36, 84%) were ≥ salvage-2 treatment status, including prior hypomethylating agent (HMA) in 77%. In combination with VEN, most patients received HMA therapy (n = 31, 72%); eight (19%) received low-dose cytarabine (LDAC). Patients received a median of 2 treatment cycles (range, 1–4). Objective response was observed in 9 (21%) patients, including 2 complete responses (CR), 3 CRi, and 4 morphologic leukemia-free state (MLFS). Median survival was 3.0 months (range, 0.5–8.0), and estimated 6-month survival was 24%. Responses were observed in five (24%) of 21 patients with intermediate-risk cytogenetics, 3 (27%) of 11 IDH1/2-mutant, and 4 (50%) of 8 RUNX1-mutated patients. Two (20%) of 10 TP53-mutated patients responded; both had concurrent RUNX1 mutations. Of the 3 (15%) responding patients with adverse cytogenetics, all had concurrent RUNX1 mutations. Conclusion: Low-intensity chemotherapy, including HMAs or LDAC, in combination with VEN is a viable salvage option, even in multiply relapsed/refractory patients with AML, MDS, and BPDCN. Notable responses were identified in patients with diploid/intermediate cytogenetics, RUNX1, and/or IDH1/2 mutations.
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U2 - 10.1002/ajh.25000
DO - 10.1002/ajh.25000
M3 - Article
C2 - 29218851
AN - SCOPUS:85038936630
SN - 0361-8609
VL - 93
SP - 401
EP - 407
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 3
ER -