Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial
Mené en Chine sur 33 patients adultes atteints d'une leucémie myéloïde aiguë (âge : 18-60 ans ; durée médiane de suivi : 11 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de rémission complète, et la toxicité d'une chimiothérapie d'induction combinant daunorubicine, cytarabine et vénétoclax
Background : Adults with acute myeloid leukaemia have unsatisfactory clinical outcomes and ratesof complete remission. Venetoclax combined with azacytidine or low-dose cytarabinehas shown efficacy in adults aged 75 years or older (or 18–74 years with comorbiditiesprecluding intensive chemotherapy) with acute myeloid leukaemia. We aimed to investigatethe activity and safety of venetoclax plus 3+7 daunorubicin and cytarabine chemotherapy in adults with acute myeloid leukaemia.
Methods : We conducted a two-stage, single-arm, phase 2 trial at three public hospitals in China.We enrolled patients aged 18–60 years with previously untreated de novo acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0–2. Patients received induction treatment with intravenous daunorubicin (60 mg/m2 on days 1–3), intravenous cytarabine (100 mg/m2 on days 1–7), and oral venetoclax (100 mg on day 4, 200 mg on day 5, and 400 mg ondays 6–11; DAV regimen). For induction therapy, the length of the treatment was 28–35days per cycle and the number of treatment cycles was one or two. The primary endpoint was the composite complete remission rate (complete remission plus complete remissionwith incomplete blood cell count recovery) after one cycle of induction treatment,assessed in the as-treated population. Secondary endpoints were bone marrow measurableresidual disease by flow cytometry, event-free survival, overall survival, and adverseevents. This trial is ongoing and is registered with Chinese Clinical Trial Registry,ChiCTR2000041509.
Findings : Between Dec 25, 2020, and July 7, 2021, 36 patients were assessed for eligibility and 33 were enrolled. 15 (45%) patients were men and 18 (55%) were women, and allwere Asian. The composite complete remission rate after one cycle of DAV regimen was91% (95% CI 76–98; 30 of 33 patients) in the entire cohort. 29 (97%) of 30 patientswho reached complete remission had undetectable measurable residual disease (ie, <0·1%).Grade 3 or worse adverse events included neutropenia in 33 (100%) of 33 patients,thrombocytopenia in 33 (100%), anaemia in 33 (100%), febrile neutropenia in 18 (55%),pneumonia in seven (21%), and sepsis in four (12%). No treatment-related deaths occurred.With a median follow-up of 11 months (IQR 9–12), estimated 1-year overall survivalwas 97% (95% CI 91–100) and 1-year event-free survival was 72% (56–94).
Interpretation : The DAV regimen represents an effective induction therapy for newly diagnosed adults with acute myeloid leukaemia, which resulted in a high rate of complete remission.These findings are an important contribution to the field, showing a safe strategyto incorporate venetoclax into the most common induction regimen used to treat newlydiagnosed acute myeloid leukaemia internationally.
The Lancet Haematology , résumé, 2021