TY - JOUR
T1 - A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for older patients with AML
AU - Zeidan, Amer M.
AU - Boss, Isaac
AU - Beach, C. L.
AU - Copeland, Wilbert B.
AU - Thompson, Ethan
AU - Fox, Brian A.
AU - Hasle, Vanessa E.
AU - Hellmann, Andrzej
AU - Taussig, David C.
AU - Tormo, Mar
AU - Voso, Maria Teresa
AU - Cavenagh, James
AU - O’Connor, Tim
AU - Previtali, Alessandro
AU - Rose, Shelonitda
AU - Silverman, Lewis R.
N1 - Funding Information:
This trial (NCT02775903) was sponsored by Celgene, a Bristol Myers Squibb company, and supported by AstraZeneca/ MedImmune.
Publisher Copyright:
© 2022 by The American Society of Hematology.
PY - 2022/4/12
Y1 - 2022/4/12
N2 - Evidence suggests that combining immunotherapy with hypomethylating agents may enhance antitumor activity. This phase 2 study investigated the activity and safety of durvalumab, a programmed death-ligand 1 (PD-L1) inhibitor, combined with azacitidine for patients aged $65 years with acute myeloid leukemia (AML), including analyses to identify biomarkers of treatment response. Patients were randomized to first-line therapy with azacitidine 75 mg/m2 on days 1 through 7 with (Arm A, n 5 64) or without (Arm B, n 5 65) durvalumab 1500 mg on day 1 every 4 weeks. Overall response rate (complete response [CR] 1 CR with incomplete blood recovery) was similar in both arms (Arm A, 31.3%; Arm B, 35.4%), as were overall survival (Arm A, 13.0 months; Arm B, 14.4 months) and duration of response (Arm A, 24.6 weeks; Arm B, 51.7 weeks; P 5 .0765). No new safety signals emerged with combination treatment. The most frequently reported treatment-emergent adverse events were constipation (Arm A, 57.8%; Arm B, 53.2%) and thrombocytopenia (Arm A, 42.2%; Arm B, 45.2%). DNA methylation, mutational status, and PD-L1 expression were not associated with response to treatment. In this study, first-line combination therapy with durvalumab and azacitidine in older patients with AML was feasible but did not improve clinical efficacy compared with azacitidine alone. ClinicalTrials.gov: NCT02775903.
AB - Evidence suggests that combining immunotherapy with hypomethylating agents may enhance antitumor activity. This phase 2 study investigated the activity and safety of durvalumab, a programmed death-ligand 1 (PD-L1) inhibitor, combined with azacitidine for patients aged $65 years with acute myeloid leukemia (AML), including analyses to identify biomarkers of treatment response. Patients were randomized to first-line therapy with azacitidine 75 mg/m2 on days 1 through 7 with (Arm A, n 5 64) or without (Arm B, n 5 65) durvalumab 1500 mg on day 1 every 4 weeks. Overall response rate (complete response [CR] 1 CR with incomplete blood recovery) was similar in both arms (Arm A, 31.3%; Arm B, 35.4%), as were overall survival (Arm A, 13.0 months; Arm B, 14.4 months) and duration of response (Arm A, 24.6 weeks; Arm B, 51.7 weeks; P 5 .0765). No new safety signals emerged with combination treatment. The most frequently reported treatment-emergent adverse events were constipation (Arm A, 57.8%; Arm B, 53.2%) and thrombocytopenia (Arm A, 42.2%; Arm B, 45.2%). DNA methylation, mutational status, and PD-L1 expression were not associated with response to treatment. In this study, first-line combination therapy with durvalumab and azacitidine in older patients with AML was feasible but did not improve clinical efficacy compared with azacitidine alone. ClinicalTrials.gov: NCT02775903.
UR - http://www.scopus.com/inward/record.url?scp=85128293422&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2021006138
DO - 10.1182/bloodadvances.2021006138
M3 - Article
C2 - 34933333
AN - SCOPUS:85128293422
VL - 6
SP - 2219
EP - 2229
JO - Blood advances
JF - Blood advances
SN - 2473-9529
IS - 7
ER -