Clinical Edge Journal Scan Commentary: AML September 2021

Dr. Atallah scans the journals, so you don’t have to!

September 7, 2021|Hematology and Oncology

Clinical Edge Journal Scan: AML September 2021 (1 of 11)

BCL-2 inhibition with venetoclax has demonstrated improved survival in combination with azacitidine in older patients with Adult acute myeloid leukemia (AML) when compared to azacitidine only. This month, a study by Kadia et al has demonstrated impressive results in younger patients with AML treated with a chemotherapy combination with venetoclax. The addition of venetoclax to intensive chemotherapy with cladribine, idarubicin, and high-dose cytarabine (CLIA regimen) was safe and feasible as frontline therapy in patients aged 65 years or younger with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Venetoclax was given for 7 days only.

Of the 50 patients enrolled, 90%, 8% and 2% had newly diagnosed AML, myelodysplastic syndrome and mixed phenotype acute leukemia respectively. Overall, 94% (95% confidence interval [CI], 83%-98%) had a composite complete response and 82% (95% CI, 68%-92%) achieved measurable residual disease negativity. At 12 months, the rates of duration of response, overall survival, and event-free survival were 74% (95% CI, 60%-92%), 85% (95% CI, 75%-97%), and 68% (95% CI, 54%-85%), respectively. The most common grade 3 or worse adverse events were febrile neutropenia (84%), infection (12%), and alanine aminotransferase elevations (12%). Only one patient had a p53 mutation and that patient did not respond. Another study by Alwash et al, demonstrated that 15% of patients acquire a TP53 mutation during AML therapy.

The poor prognosis of patients with a p53 ,mutation was also seen in a retrospective study of patients with newly diagnosed or relapsed/refractory AML treated with 10-day decitabine + venetoclax (DEC10-VEN). Of the 118 patients, 35 had a TP53 mutation. Complete remission/complete remission with incomplete count recovery (57% vs 775), and overall response was better for patients without vs with a TP53 mutation. In addition, overall survival was dismal (5.2 months) for patients with TP53 mutation vs those without (19.4 months).

This study reiterates the need for newer therapies for this group of patients with a TP53 mutation (Kim K et al). The overall outcome of patients treated with DEC10-VEN was better compared to intensive chemotherapy (IC) in patients with relapsed refractory AML. This was evaluated in a retrospective study assessing the outcomes of adult patients with R/R AML treated with DEC10-VEN (n=65) a vs IC-based regimen (n=130) using propensity score-matched analysis. Patients receiving DEC10-VEN vs IC had superior overall response rate (odds ratio [OR], 3.28; P < .001), minimal residual disease negativity (OR, 2.48; P = .017), event-free survival (hazard ratio [HR], 0.46; P < .001), and overall survival (HR, 0.56; P = .008). Rates of refractory disease (OR, 0.46; P = .011) and 60-day mortality (OR, 0.40; P = .029) were significantly lower in patients receiving DEC10-VEN vs IC.