Characteristics of molecular HGBL in studies using GEP for patients diagnosed as having DLBCL
| Characteristic . | (REMoDL-B)43 N = 928 . | (BCCA)44 N = 157 (GCB only) . |
|---|---|---|
| Study cohort | Phase 3 clinical trial | Observational cohort |
| Molecular HGBL, n (%) | 83 (9) | 42 (27) |
| Median age, y | 65 | 62 |
| Stage III/IV, n (%) | 63 (76) | 23 (56) |
| LDH | Median, 561 units/L | 58% elevated |
| Extranodal involvement, n (%) | 53 (64) | NR; 7% >1 site |
| High IPI, n (%) | 25 (30) | 7 (17) |
| GCB by GEP, % | 90 | 100 (by definition) |
| Cytogenetics, n (%) MYC-R Double/triple hit | 35 (49) 26 (36) | 27 (64) 22 (52) |
| Immunohistochemistry, n (%) | ||
| MYC+ BCL2+ MYC+/BCL2+ | 20 (71) 22 (79) 17 (61) | 30 (75) 36 (88) 25 (63) |
| PFS or TTP, % | 37 at 3 y (R-CHOP) vs 78 in GCB DLBCL vs 64 in ABC DLBCL | 57 at 5 y vs 81 in GCB DLBCL vs 51 in ABC DLBCL |
| OS, % | 57 at 3 y (all patients) vs 88 in GCB DLBCL vs 81 in ABC DLBCL | 60 at 5 y vs 81 in GCB DLBCL vs 56 in ABC DLBCL |
| GEP signature | Trained on BL vs DLBCL ↑ MYC, TCF3 targets ↓ MHC-II ↓ immune response ↓ inflammation | Trained on DHL vs DLBCL ↑ MYC, E2F targets ↓ MHC-I and MHC-II ↑ oxidative phosphorylation ↓ TNFα, NF-κB, IL-6/JAK/STAT3 |
| Mutations | MYC, BCL2, TP53, EZH2, DDX3X, KMT2D | MYC, BCL2, TP53, EZH2, DDX3X, KMT2D, CREBBP |
| Characteristic . | (REMoDL-B)43 N = 928 . | (BCCA)44 N = 157 (GCB only) . |
|---|---|---|
| Study cohort | Phase 3 clinical trial | Observational cohort |
| Molecular HGBL, n (%) | 83 (9) | 42 (27) |
| Median age, y | 65 | 62 |
| Stage III/IV, n (%) | 63 (76) | 23 (56) |
| LDH | Median, 561 units/L | 58% elevated |
| Extranodal involvement, n (%) | 53 (64) | NR; 7% >1 site |
| High IPI, n (%) | 25 (30) | 7 (17) |
| GCB by GEP, % | 90 | 100 (by definition) |
| Cytogenetics, n (%) MYC-R Double/triple hit | 35 (49) 26 (36) | 27 (64) 22 (52) |
| Immunohistochemistry, n (%) | ||
| MYC+ BCL2+ MYC+/BCL2+ | 20 (71) 22 (79) 17 (61) | 30 (75) 36 (88) 25 (63) |
| PFS or TTP, % | 37 at 3 y (R-CHOP) vs 78 in GCB DLBCL vs 64 in ABC DLBCL | 57 at 5 y vs 81 in GCB DLBCL vs 51 in ABC DLBCL |
| OS, % | 57 at 3 y (all patients) vs 88 in GCB DLBCL vs 81 in ABC DLBCL | 60 at 5 y vs 81 in GCB DLBCL vs 56 in ABC DLBCL |
| GEP signature | Trained on BL vs DLBCL ↑ MYC, TCF3 targets ↓ MHC-II ↓ immune response ↓ inflammation | Trained on DHL vs DLBCL ↑ MYC, E2F targets ↓ MHC-I and MHC-II ↑ oxidative phosphorylation ↓ TNFα, NF-κB, IL-6/JAK/STAT3 |
| Mutations | MYC, BCL2, TP53, EZH2, DDX3X, KMT2D | MYC, BCL2, TP53, EZH2, DDX3X, KMT2D, CREBBP |
ABC, activated B cell; BCCA, British Columbia Cancer Agency; IL-6, interleukin-6; IPI, International prognostic index; NR, not reported; TNFα, tumor necrosis factor α; TTP, time to progression.