Complete Remission With Partial Hematological Recovery Shows Benefit as Palliative End Point for Nonmyelosuppressive Treatment of Patients With AML

According to a recent analysis reported in Blood, the achievement of complete remission with partial hematological recovery (CRh) as an outcome correlated with benefits consistent with clinically meaningful palliative effects for the treatment of patients with acute myeloid leukemia (AML) with non-myelosuppressive drugs. Though clinically meaningful as an outcome measure, CRh was still found to be inferior to complete remission (CR).

“[CRh] has been used as an efficacy end point in clinical trials of non-myelosuppressive drugs for AML,” stated first study author Robert Le, MD, PhD, US Food and Drug Administration, Silver Spring, Maryland, and colleagues.

Investigators conducted a pooled analysis to characterize the clinical outcomes for patients with AML who achieved CRh following ivosidenib, olutasidenib, enasidenib, or gilteritinib monotherapy treatment in clinical trials used to support marketing applications. The cohort included 841 adult patients who were treated at the recommended drug dosage, and 64.6% of patients were red blood cell or platelet transfusion dependent at study baseline.

Analysis results demonstrated that patients with CRh exhibited a higher proportion with transfusion independence (TI) for at least 56 days (TI-56; 92.3% vs 22.3%; P < .0001) or TI for at least 112 days (TI-112; 63.5% vs 8.7%; P < .0001), a reduced risk over time for severe infection (hazard ratio [HR], 0.43; P = .0007) or severe bleeding (HR, 0.17; P = .01), in addition to a longer overall survival (OS; HR, 0.31; P < .0001) than patients with no response. The effects were consistent across the monotherapy treatment regimens. In comparison with patients with CR, the effect sizes for CRh were similar for TI-56 and for risk over time of infection or bleeding but measured less for TI-112 and OS. 

“CRh is associated with clinical benefits consistent with clinically meaningful palliative effects for the treatment of AML with non-myelosuppressive drugs, although less robustly than for CR,” concluded Dr Le and coauthors.

Source:

Le R, Przepiorka D, Chen H, et al. Complete remission with partial hematological recovery as a palliative end point for treatment of acute myeloid leukemia. Published online July 11, 2024. doi: 10.1182/blood.2023023313