Table 3.

Immune correlatives of immunotherapy success and failure in AML

Study	Treatment	Disease	Number of patients, N	Immune correlates	Trial ID
Davids et al71	Ipilimumab	Post-HSCT relapse	28	Infiltration of cytotoxic CD8+ T cells, decreased activation of Treg cells, and expansion of effector T cells in responders	NCT01822509
Daver et al72	Azacitidine + nivolumab	R/R AML	70	Pretherapy BM CD3+ and CD8+ T cells associate with improved ORR Th17 cell expansion in nonresponders	NCT02397720
Vadakekolathu et al9 and Uy et al10	Flotetuzumab	R/R AML	88 (15 with TP53 mutations)	TIS higher at baseline in responders	NCT02152956
Zeidner et al73	High-dose cytarabine + pembrolizumab	R/R AML	37	Higher frequency of CD8+ TPEX expressing TCF-1 at baseline in responders	NCT02768792
Abbas et al37	Azacitidine + nivolumab	R/R AML	8	Higher abundance of CD8+GZMK+TCF7+ T cells in responders Loss of chr7/7q associated with NR	NCT02397720
Goswami et al74	Decitabine + pembrolizumab	R/R AML	10	irAEs linked to clonal expansions of CD8+PD1+ effector T cells	NCT02996474
Rutella et al55	Azacitidine + pembrolizumab	R/R AML	33	Dysfunctional NK-like CD8+ T cells associated with NR to pembrolizumab	NCT02845297
Rimando et al75	Azacitidine + pembrolizumab High-dose cytarabine + pembrolizumab	Newly diagnosed and R/R AML	31 18	Differentiated blasts (promonocytic profile) expanded in responders	NCT02845297 NCT02768792
Garcia et al76	Decitabine + ipilimumab	R/R AML (after HSCT and HSCT naive)	54	Immune activation (irAEs) associated with survival benefit	NCT02890329
Penter et al77	Decitabine + ipilimumab	R/R AML (after HSCT and HSCT naive)	18	Altered CD4+ T-cell gene expression after ipilimumab. Increased infiltration with antigen–experienced resident memory T cells in leukemia cutis samples from responders.	NCT02890329

irAEs, immune-related adverse events; NR, no response; ORR, overall response rate; TCF-1, T-cell factor 1; TIS, tumor inflammation signature.