Clinical trials in DLBCL with SCNSL
| Study . | Regimen . | Primary end point . | Histology . | N . | Presentation, % . | Median age (range), y . | ASCT conditioning . | Response, % . | Survival, % . | TRM, % . |
|---|---|---|---|---|---|---|---|---|---|---|
| 1. MARIETTA5 | MATRix × 3 R-ICE × 3 Liposomal Ara-C or triple IT | 1-y PFS | DLBCL | 75 | De novo, 43 CNS relapse, 20 CNS-systemic relapse, 37 | 58 (23-70) | Carmustine Thiotepa | ORR, 61 CR, 55 | 1-y PFS, 58 2-y OS, 46 | 5 |
| 2. SCNSL124 | HD-MTX and Ara-C R-HDS Liposomal Ara-C IT | 2-y EFS | DLBCL, 84% MCL, 8% FL gr 3, 8% | 38 | De novo, 42 CNS relapse, 40 CNS-systemic relapse, 18 | 59 (36-70) | Carmustine Thiotepa | ORR, 63 CR, 63 | 2-y EFS, 50 5-y OS, 41 | 10 |
| 3. NCT0114817325 | HD-MTX and ifosfamide Ara-C and thiotepa Liposomal Ara-C IT | TTF | DLBCL, 90% PTCL, 10% | 30 | CNS relapse, 80 CNS-systemic relapse, 20 | 58 (29-65) | Carmustine Thiotepa Etoposide | ORR, 71 CR, 63 | 2-y TTF, 49 2-y OS, 63 | 3 |
| 4. HOVON 8026 | R-DHAP × 3 HD-MTX × 3 Rituximab IT | 1-y PFS | DLBCL, 97% FL gr 3, 3% | 36 | CNS relapse, 44 CNS-systemic relapse, 56 | 57 (23-65) | Busulfan Cyclophosphamide | ORR, 53 CR, 22 | 1-y PFS, 19 1-y OS, 25 | 5 |
| 5. UK NCRI27 | R-CODOX-M/IVAC | 2-y PFS | DLBCL | 10 | De novo, 100 | 50∗ (18-65) | — | ORR, 74∗ CR, 47 | 2-y PFS, 70 | 4∗ |
| 6. NCT0231532628 | Ibrutinib, HD-MTX, and rituximab | MTD | DLBCL | 6 | De novo, 50 CNS relapse, 50 | 62∗ (23-74) | - | ORR, 67 CR, 33 | 1-y OS, 71∗ | 0 |
| 7. NCT0396409029 | TEDDI-R | PFS | DLBCL, 55% HGBL, 33% | 49 | De novo, 10 CNS relapse, 90 | 62 (26-89) | - | ORR, 92†, CR, 77† | 1-y PFS, 37 1-y OS, 61 | 2 |
| Study . | Regimen . | Primary end point . | Histology . | N . | Presentation, % . | Median age (range), y . | ASCT conditioning . | Response, % . | Survival, % . | TRM, % . |
|---|---|---|---|---|---|---|---|---|---|---|
| 1. MARIETTA5 | MATRix × 3 R-ICE × 3 Liposomal Ara-C or triple IT | 1-y PFS | DLBCL | 75 | De novo, 43 CNS relapse, 20 CNS-systemic relapse, 37 | 58 (23-70) | Carmustine Thiotepa | ORR, 61 CR, 55 | 1-y PFS, 58 2-y OS, 46 | 5 |
| 2. SCNSL124 | HD-MTX and Ara-C R-HDS Liposomal Ara-C IT | 2-y EFS | DLBCL, 84% MCL, 8% FL gr 3, 8% | 38 | De novo, 42 CNS relapse, 40 CNS-systemic relapse, 18 | 59 (36-70) | Carmustine Thiotepa | ORR, 63 CR, 63 | 2-y EFS, 50 5-y OS, 41 | 10 |
| 3. NCT0114817325 | HD-MTX and ifosfamide Ara-C and thiotepa Liposomal Ara-C IT | TTF | DLBCL, 90% PTCL, 10% | 30 | CNS relapse, 80 CNS-systemic relapse, 20 | 58 (29-65) | Carmustine Thiotepa Etoposide | ORR, 71 CR, 63 | 2-y TTF, 49 2-y OS, 63 | 3 |
| 4. HOVON 8026 | R-DHAP × 3 HD-MTX × 3 Rituximab IT | 1-y PFS | DLBCL, 97% FL gr 3, 3% | 36 | CNS relapse, 44 CNS-systemic relapse, 56 | 57 (23-65) | Busulfan Cyclophosphamide | ORR, 53 CR, 22 | 1-y PFS, 19 1-y OS, 25 | 5 |
| 5. UK NCRI27 | R-CODOX-M/IVAC | 2-y PFS | DLBCL | 10 | De novo, 100 | 50∗ (18-65) | — | ORR, 74∗ CR, 47 | 2-y PFS, 70 | 4∗ |
| 6. NCT0231532628 | Ibrutinib, HD-MTX, and rituximab | MTD | DLBCL | 6 | De novo, 50 CNS relapse, 50 | 62∗ (23-74) | - | ORR, 67 CR, 33 | 1-y OS, 71∗ | 0 |
| 7. NCT0396409029 | TEDDI-R | PFS | DLBCL, 55% HGBL, 33% | 49 | De novo, 10 CNS relapse, 90 | 62 (26-89) | - | ORR, 92†, CR, 77† | 1-y PFS, 37 1-y OS, 61 | 2 |
Studies 1 to 4 exclusively enrolled patients with SCNSL. Study 5 enrolled 111 patients with untreated DLBCL, including 10 (9%) patients with SCNSL. Study 6 was a phase 1b trial that enrolled 15 patients with PCNSL (n = 9; 60%) and SCNSL (n = 6; 40%).
Ara-C, cytarabine; EFS, event-free survival; FL, follicular lymphoma; gr, grade; HD, high-dose; PTCL, peripheral T-cell lymphoma; R-DHS, rituximab, cyclophosphamide, cytarabine, and etoposide; TEDDI-R, temozolomide, etoposide, liposomal doxorubicin, dexamethasone, ibrutinib, rituximab; TRM, treatment-related mortality; TTF, time-to-treatment failure; MTD, maximum tolerated dose.
Data from the entire study cohort.
In 26 patients with response to ibrutinib.