TY - JOUR
T1 - A multi-arm phase Ib/II study designed for rapid, parallel evaluation of novel immunotherapy combinations in relapsed/refractory acute myeloid leukemia
AU - Short, Nicholas J.
AU - Borthakur, Gautam
AU - Pemmaraju, Naveen
AU - Dinardo, Courtney D.
AU - Kadia, Tapan M.
AU - Jabbour, Elias
AU - Konopleva, Marina
AU - Macaron, Walid
AU - Ning, Jing
AU - Ma, Junsheng
AU - Pierce, Sherry
AU - Alvarado, Yesid
AU - Sasaki, Koji
AU - Takahashi, Koichi
AU - Estrov, Zeev
AU - Masarova, Lucia
AU - Issa, Ghayas C.
AU - Montalban-Bravo, Guillermo
AU - Andreeff, Michael
AU - Burger, Jan A.
AU - Miller, Darla
AU - Alexander, Lynette
AU - Naing, Aung
AU - Garcia-Manero, Guillermo
AU - Ravandi, Farhad
AU - Daver, Naval
N1 - Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - We conducted a phase Ib/II multi-arm, parallel cohort study to simultaneously evaluate various immunotherapeutic agents and combinations in relapsed/refractory acute myeloid leukemia (AML). Overall, 50 patients were enrolled into one of 6 arms: (A) single agent PF-04518600 (OX40 agonist monoclonal antibody), (B) azacitidine + venetoclax + gemtuzumab ozogamicin (GO), (C) azacitidine + avelumab (anti-PD-L1 monoclonal antibody) + GO, (D) azacitidine + venetoclax + avelumab, (E) azacitidine + avelumab + PF-04518600, and (F) glasdegib + GO. Among all regimens evaluated, azacitidine + venetoclax + GO appeared most promising. In this arm, the CR/CRi rates among venetoclax-naïve and prior venetoclax-exposed patients were 50% and 22%, respectively, and the 1-year OS rate was 31%. This study shows the feasibility of a conducting a multi-arm trial to efficiently and simultaneously evaluate novel therapies in AML, a needed strategy in light of the plethora of emerging therapies. This trial was registered at www.clinicaltrials.gov as NCT03390296.
AB - We conducted a phase Ib/II multi-arm, parallel cohort study to simultaneously evaluate various immunotherapeutic agents and combinations in relapsed/refractory acute myeloid leukemia (AML). Overall, 50 patients were enrolled into one of 6 arms: (A) single agent PF-04518600 (OX40 agonist monoclonal antibody), (B) azacitidine + venetoclax + gemtuzumab ozogamicin (GO), (C) azacitidine + avelumab (anti-PD-L1 monoclonal antibody) + GO, (D) azacitidine + venetoclax + avelumab, (E) azacitidine + avelumab + PF-04518600, and (F) glasdegib + GO. Among all regimens evaluated, azacitidine + venetoclax + GO appeared most promising. In this arm, the CR/CRi rates among venetoclax-naïve and prior venetoclax-exposed patients were 50% and 22%, respectively, and the 1-year OS rate was 31%. This study shows the feasibility of a conducting a multi-arm trial to efficiently and simultaneously evaluate novel therapies in AML, a needed strategy in light of the plethora of emerging therapies. This trial was registered at www.clinicaltrials.gov as NCT03390296.
KW - avelumab
KW - azacitidine
KW - gemtuzumab ozogamicin
KW - Monoclonal antibody
KW - venetoclax
UR - http://www.scopus.com/inward/record.url?scp=85129353584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129353584&partnerID=8YFLogxK
U2 - 10.1080/10428194.2022.2062345
DO - 10.1080/10428194.2022.2062345
M3 - Article
C2 - 35442137
AN - SCOPUS:85129353584
SN - 1042-8194
VL - 63
SP - 2161
EP - 2170
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 9
ER -