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 |
| 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.