scholarly journals A Randomized Phase 2 Trial of Azacitidine ± Durvalumab as First-line Therapy for Higher-Risk Myelodysplastic Syndromes

Author(s):  
Amer M. Zeidan ◽  
Isaac Wayne Boss ◽  
CL Beach ◽  
Wilbert B. Copeland ◽  
Ethan Greene Thompson ◽  
...  

Azacitidine-mediated hypomethylation promotes tumor cell immune recognition but may increase inhibitory immune checkpoint (ICP) molecule expression. We conducted the first randomized phase 2 study of azacitidine plus the ICP inhibitor durvalumab versus azacitidine monotherapy as first-line treatment of higher-risk myelodysplastic syndromes (HR-MDS). Patients (N=84) received azacitidine 75 mg/m2 subcutaneously (days 1-7) with (Arm A) or without (Arm B) durvalumab 1500 mg intravenously on day 1 every 4 weeks. After a median follow-up of 15.25 months, 8 patients in Arm A and 6 in Arm B remained on treatment. Patients in Arms A and B received a median of 7.9 and 7.0 treatment cycles, respectively, with 73.7% and 65.9% completing ≥4 cycles. The overall response rate (primary endpoint) was 61.9% in Arm A (26/42) and 47.6% in Arm B (20/42; P=0.18), and median overall survival was 11.6 months (95% CI: 9.5, nonevaluable) versus 16.7 months (95% CI: 9.8, 23.5) (P=0.74). Durvalumab-related adverse events (AEs) were reported by 71.1% of patients; azacitidine-related AEs were reported by 82% (A) and 81% (B). Grade 3 or 4 hematologic AEs were reported in (Arm A vs B) 89.5% vs 68.3% of patients. Patients with TP53 mutations tended to have a worse response than patients without these mutations. Azacitidine increased PD-L1 (CD274) surface expression on bone marrow granulocytes and monocytes, but not blasts, in both arms. In summary, combining durvalumab and azacitidine in patients with HR-MDS was feasible, but with more toxicities and without significant improvement in clinical outcomes over azacitidine alone. ClinicalTrials.gov: NCT02775903

Cancer ◽  
2013 ◽  
Vol 119 (14) ◽  
pp. 2555-2563 ◽  
Author(s):  
Jeffrey R. Infante ◽  
Tony R. Reid ◽  
Allen L. Cohn ◽  
William J. Edenfield ◽  
Terrence P. Cescon ◽  
...  

2021 ◽  
Author(s):  
Juan‐Manuel Sancho ◽  
Rubén Fernández‐Alvarez ◽  
Francisco Gual‐Capllonch ◽  
Esther González‐García ◽  
Carlos Grande ◽  
...  

2016 ◽  
Vol 27 ◽  
pp. vi582 ◽  
Author(s):  
C. Langer ◽  
S.M. Gaddgeel ◽  
H. Borghaei ◽  
V.A. Papadimitrakopoulou ◽  
A. Patnaik ◽  
...  

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