Clinical experience with the BCL2‐inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies. Issue 3 (23rd December 2017)

• Record Type: Journal Article
• Authors: DiNardo, Courtney D.; Rausch, Caitlin R.; Benton, Christopher; Kadia, Tapan; Jain, Nitin; Pemmaraju, Naveen; Daver, Naval; Covert, Wendy; Marx, Kayleigh R.; Mace, Morgan; Jabbour, Elias; Cortes, Jorge; Garcia‐Manero, Guillermo; Ravandi, Farhad; Bhalla, Kapil N.; Kantarjian, Hagop; Konopleva, Marina
• Is Part Of: American journal of hematology. Volume 93:Issue 3(2018:Mar.)
• Page Start: 401
• Page End: 407
• Publication Date: 2017-12-23
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.25000
• Languages: English
• ISSNs: 0361-8609

Abstract

Abstract: 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.