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Venetoclax With Low-Dose Cytarabine Demonstrates Efficacy, Tolerability for Patients With AML at First MRD or Oligoblastic Relapse
According to phase 2 results from a prospective study, venetoclax combined with low-dose cytarabine (LDAC) is well tolerated and highly effective among patients with acute myeloid leukemia (AML) at first measurable residual disease (MRD) or oligoblastic relapse.
This prospective study included 26 patients with MRD (≥1 log10 rise) and 22 patients with oligoblastic relapse (blasts 5% to 15%) who received venetoclax 600 mg once daily, days 1 to 28 plus LDAC once daily days 1 to 10 in 28-day cycles. It was noted that 94% of enrolled patients had received previous intensive chemotherapy. The primary objective was MRD response in the MRD relapse cohort or complete remission (CR/CRh/CRi) in the oligoblastic relapse cohort.
Trial participants received a median of 4 cycles of therapy; 17% of patients completed ≥12 cycles. The molecular markers of MRD relapse in this study included mutant NPM1 (77%), CBFB::MYH11 (4%), RUNX1::RUNX1T1 (4%), or KMT2A::MLLT3 (4%). It was noted that 3 patients with a log10 rise in IDH1/2 (12%) were included.
Results demonstrated that by cycle 2 in the MRD relapse cohort, a log10 reduction in MRD was observed in 69% of patients; 46% achieved MRD negative remission. In the oligoblastic relapse cohort, 73% of study participants achieved CR/CRh/CRi. Overall, 21 (44%) patients underwent hematopoietic cell transplantation (HCT). The measured median overall survival (OS) was not reached in either cohort, and the estimated 2-year OS rate was 67% (95% [confidence interval] CI, 50 to 89) in the MRD and 53% (95% CI, 34 to 84) in the oligoblastic relapse cohorts.
Investigators noted that survival appeared higher among patients with MRD clearance, which suggested the relevance of improved response depth for optimized outcomes. Additionally, study results indicated that post-HCT outcomes after venetoclax-LDAC were encouraging.
The following safety measurements were observed: Patients with oligoblastic relapse had more grade ≥3 anemia (32% vs 4%; P = .02) and infections (36% vs 8%; P = .03), whereas grade 4 neutropenia (32 vs 23%) or thrombocytopenia (27 vs 15%) were comparable with those in the MRD relapse cohort.
Ing Soo Tiong, MBChB, MPhil, FRACP, FRCPA, The Alfred Hospital and Monash University, Melbourne, Australia, and colleagues concluded, “…To our knowledge, this is the first prospective study of venetoclax-LDAC at first MRD or oligoblastic relapse, confirming feasibility, safety, and promising efficacy, especially for NPM1MUT AML.”
The study authors also noted, “Future studies are needed to determine the utility of pre-HCT MRD eradication compared with directly proceeding to HCT and the ability of MRD-directed intervention to alter the natural history of disease, compared with treatment at morphologic relapse.”
Source:
Tiong I, Hiwase D, Abro E, et al. Targeting molecular measurable residual disease and low-blast relapse in AML with venetoclax and low-dose cytarabine: A prospective phase II study (VALDAC). JCO 0, JCO.23.01599. doi:10.1200/JCO.23.01599
