Q3 2022: Additional information and data in acute leukemia

July 27, 2022

AML

The combination of the IDH1 inhibitor ivosidenib and azacitidine demonstrated significant clinical benefit in patients with newly diagnosed IDH1-mutated AML, according to phase III results published in The New England Journal of MedicineWith a median follow-up of just more than one year, the median event-free survival (EFS) was significantly longer for patients treated with ivosidenib plus azacitidine compared with those treated with azacitidine plus placebo (hazard ratio for treatment failure, relapse from remission, or death = 0.33; 95% CI 0.16-0.69; p=0.002). (Ref. Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemiaN Engl J Med. 2022;386:1519-1531.)

ALL

Combination treatment with the tyrosine kinase inhibitor nilotinib and anti–PD-L1 dramatically improves long-term survival of leukemic mice. Depletion of CD4+ T cells prior to therapy completely abrogates the survival benefit, implicating CD4+ T cells as key drivers of the protective anti-leukemia immune response. Indeed, treatment with anti–PD-L1 leads to clonal expansion of leukemia-specific CD4+ T cells with the aforementioned helper/cytotoxic phenotype as well as reduced expression of exhaustion markers. These findings support efforts to use PD1/PD-L1 checkpoint blockade in clinical trials and highlight the importance of CD4+ T-cell dysfunction in limiting the endogenous anti-leukemia response. (Ref: https://doi.org/10.1182/blood.2021015341)