Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: phase 3 randomized placebo-controlled trial
Standard
Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: phase 3 randomized placebo-controlled trial. / Wei, Andrew Henry; Montesinos, Pau; Ivanov, Vladimir; DiNardo, Courtney D; Novak, Jan; Laribi, Kamel; Kim, Inho; Stevens, Don; Fiedler, Walter; Pagoni, Maria; Samoilova, Olga; Hu, Yu; Anagnostopoulos, Achilles; Bergeron, Julie; Hou, Jing-Zhou; Murthy, Vidhya; Yamauchi, Takahiro; McDonald, Andrew Bruce; Chyla, Brenda; Gopalakrishnan, Sathej; Jiang, Qi; Mendes, Wellington L; Hayslip, John; Panayiotidis, Panayiotis.
In: BLOOD, Vol. 135, No. 24, 11.06.2020, p. 2137-2145.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: phase 3 randomized placebo-controlled trial
AU - Wei, Andrew Henry
AU - Montesinos, Pau
AU - Ivanov, Vladimir
AU - DiNardo, Courtney D
AU - Novak, Jan
AU - Laribi, Kamel
AU - Kim, Inho
AU - Stevens, Don
AU - Fiedler, Walter
AU - Pagoni, Maria
AU - Samoilova, Olga
AU - Hu, Yu
AU - Anagnostopoulos, Achilles
AU - Bergeron, Julie
AU - Hou, Jing-Zhou
AU - Murthy, Vidhya
AU - Yamauchi, Takahiro
AU - McDonald, Andrew Bruce
AU - Chyla, Brenda
AU - Gopalakrishnan, Sathej
AU - Jiang, Qi
AU - Mendes, Wellington L
AU - Hayslip, John
AU - Panayiotidis, Panayiotis
N1 - © 2020 by The American Society of Hematology.
PY - 2020/6/11
Y1 - 2020/6/11
N2 - Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.
AB - Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.
U2 - 10.1182/blood.2020004856
DO - 10.1182/blood.2020004856
M3 - SCORING: Journal article
C2 - 32219442
VL - 135
SP - 2137
EP - 2145
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 24
ER -