Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC)

Tiong, IS; Hiwase, DK; Abro, E; Bajel, A; Palfreyman, E; Beligaswatte, A; Reynolds, J; Anstee, N; Nguyen, T; Loo, S; Chua, CC; Ashby, M; Wiltshire, KM; Fleming, S; Fong, CY; Teh, TC; Blombery, P; Dillon, R; Ivey, A; Wei, AH

Author(s): Tiong, IS; Hiwase, DK; Abro, E; Bajel, A; Palfreyman, E; Beligaswatte, A; Reynolds, J; Anstee, N; Nguyen, T; Loo, S; Chua, CC; Ashby, M; Wiltshire, KM; Fleming, S; Fong, CY; Teh, TC; Blombery, P; Dillon, R; Ivey, A; Wei, AH;
Details: Publication Year 2024-06-20,Volume 42,Issue #18,Page 2161-2173
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: PURPOSE: A prospective phase II study examined the safety and efficacy of venetoclax combined with low-dose cytarabine (LDAC) in AML at first measurable residual disease (MRD) or oligoblastic relapse. METHODS: Patients with either MRD (≥1 log(10) rise) or oligoblastic relapse (blasts 5%-15%) received venetoclax 600 mg once daily D1-28 plus LDAC once daily D1-10 in 28-day cycles. The primary objective was MRD response in the MRD relapse cohort or complete remission (CR/CRh/CRi) in the oligoblastic relapse cohort. RESULTS: Forty-eight adults with either MRD (n = 26) or oligoblastic (n = 22) relapse were enrolled. Median age was 67 years (range, 18-80) and 94% had received previous intensive chemotherapy. Patients received a median of four cycles of therapy; 17% completed ≥12 cycles. Patients with oligoblastic relapse had more grade ≥3 anemia (32% v 4%; P = .02) and infections (36% v 8%; P = .03), whereas grade 4 neutropenia (32 v 23%) or thrombocytopenia (27 v 15%) were comparable with the MRD relapse cohort. Markers of molecular MRD relapse included mutant NPM1 (77%), CBFB::MYH11 (4%), RUNX1::RUNX1T1 (4%), or KMT2A::MLLT3 (4%). Three patients with a log(10) rise in IDH1/2 (12%) were included. By cycle 2 in the MRD relapse cohort, a log(10) reduction in MRD was observed in 69%; 46% achieved MRD negative remission. In the oligoblastic relapse cohort, 73% achieved CR/CRh/CRi. Overall, 21 (44%) underwent hematopoietic cell transplantation. Median overall survival (OS) was not reached in either cohort. Estimated 2-year OS rate was 67% (95% CI, 50 to 89) in the MRD and 53% (95% CI, 34 to 84) in the oligoblastic relapse cohorts. CONCLUSION: For AML in first remission and either MRD or oligoblastic relapse, venetoclax plus LDAC is well tolerated and highly effective.
Publisher: American Society of Clinical Oncology
Keywords: Humans; Aged; Middle Aged; *Leukemia, Myeloid, Acute/drug therapy/mortality/genetics/pathology; *Neoplasm, Residual; *Cytarabine/administration & dosage; *Sulfonamides/administration & dosage/adverse effects; Adult; Female; Male; *Bridged Bicyclo Compounds, Heterocyclic/administration & dosage/adverse effects; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects; Aged, 80 and over; Prospective Studies; *Nucleophosmin; Young Adult; Adolescent
Department(s): Clinical Haematology; Pathology
Publisher's Version: https://doi.org/10.1200/jco.23.01599
Open Access at Publisher's Site: https://doi.org/10.1200/jco.23.01599
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-08-27 07:27:57

Last Modified: 2024-08-27 07:28:27