TY - JOUR
T1 - Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome
AU - Gerds, Aaron T.
AU - Scott, Bart L.
AU - Greenberg, Peter
AU - Lin, Tara L.
AU - Pollyea, Daniel A.
AU - Verma, Amit
AU - Dail, Monique
AU - Feng, Yuning
AU - Green, Cherie
AU - Ma, Connie
AU - Medeiros, Bruno C.
AU - Yan, Mark
AU - Yousefi, Kasra
AU - Donnellan, William
N1 - Publisher Copyright:
© 2022 by The American Society of Hematology.
PY - 2022/2/22
Y1 - 2022/2/22
N2 - We present primary results from the phase 1b GO29754 study evaluating the safety and tolerability of atezolizumab, a programmed death-ligand 1 inhibitor, alone and in combination with azacitidine, a hypomethylating agent (HMA), in patients with relapsed/refractory (R/R) or HMA-naïve myelodysplastic syndrome (MDS). Patients with R/R MDS received atezolizumab for 12 months (cohort A) or atezolizumab plus azacitidine for 6 cycles followed by atezolizumab as maintenance for 8 cycles (cohort B). Patients with HMA-naïve MDS received atezolizumab plus azacitidine until loss of clinical benefit (cohort C). Safety, activity, and exploratory end points were investigated. Forty-six patients were enrolled and received treatment (cohort A, n 5 11; cohort B, n 5 14; cohort C, n 5 21). All patients experienced $1 adverse event (AE) on study, and all patients discontinued atezolizumab. In cohort A, 7 patients (63.6%) died, and no patients responded. In cohort B, 8 patients (57.1%) discontinued azacitidine, 11 (78.6%) died, and 2 (14.3%) responded. In cohort C, all 21 patients discontinued azacitidine, 13 died (61.9%), and 13 (61.9%) responded. The study was terminated by the sponsor before completion of recruitment because of the unexpected high early death rate in cohort C (6 [46.2%] of 13 deaths were due to AEs and occurred within the first 4 treatment cycles.). The high death rate and poor efficacy observed in this study do not support a favorable risk-benefit profile for atezolizumab as a single agent or in combination with azacitidine in R/R or HMA-naïve MDS.
AB - We present primary results from the phase 1b GO29754 study evaluating the safety and tolerability of atezolizumab, a programmed death-ligand 1 inhibitor, alone and in combination with azacitidine, a hypomethylating agent (HMA), in patients with relapsed/refractory (R/R) or HMA-naïve myelodysplastic syndrome (MDS). Patients with R/R MDS received atezolizumab for 12 months (cohort A) or atezolizumab plus azacitidine for 6 cycles followed by atezolizumab as maintenance for 8 cycles (cohort B). Patients with HMA-naïve MDS received atezolizumab plus azacitidine until loss of clinical benefit (cohort C). Safety, activity, and exploratory end points were investigated. Forty-six patients were enrolled and received treatment (cohort A, n 5 11; cohort B, n 5 14; cohort C, n 5 21). All patients experienced $1 adverse event (AE) on study, and all patients discontinued atezolizumab. In cohort A, 7 patients (63.6%) died, and no patients responded. In cohort B, 8 patients (57.1%) discontinued azacitidine, 11 (78.6%) died, and 2 (14.3%) responded. In cohort C, all 21 patients discontinued azacitidine, 13 died (61.9%), and 13 (61.9%) responded. The study was terminated by the sponsor before completion of recruitment because of the unexpected high early death rate in cohort C (6 [46.2%] of 13 deaths were due to AEs and occurred within the first 4 treatment cycles.). The high death rate and poor efficacy observed in this study do not support a favorable risk-benefit profile for atezolizumab as a single agent or in combination with azacitidine in R/R or HMA-naïve MDS.
UR - http://www.scopus.com/inward/record.url?scp=85125326008&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125326008&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2021005240
DO - 10.1182/bloodadvances.2021005240
M3 - Article
C2 - 34932793
AN - SCOPUS:85125326008
SN - 2473-9529
VL - 6
SP - 1152
EP - 1161
JO - Blood Advances
JF - Blood Advances
IS - 4
ER -