Studies evaluating HD-MTX for CNS prophylaxis in DLBCL
| Study . | Study type . | Lymphoma type/risk . | Primary treatment . | Systemic CNS prophylaxis (# cycles) . | CNS relapse . |
|---|---|---|---|---|---|
| GELA/LYSA, Tilly et al40 | Prospective phase 3 | All aggressive 80% DLBCL | 1. ACVBP 2. CHOP | 1. HDMTX 3 g/m2 (2) 2. None | 0.8%* 2.7%*P = .002 |
| Nordic, Holte et al41 | Prospective phase 2 | DLBCL (74%) FL 3A aaIPI 2-3 | DI R-CHOEP14 | AraC 3 g/m2 (1) HDMTX 3 g/m2 (1) | 4.4%* |
| UK NCRI/Bloodwise, Phillips et al42 | Prospective phase 2 | DLBCL IPI ≥3 | R-CODOX-M-R-IVAC | HDMTX 3 g/m2 (+IT) Ifosfamide, AraC (+IT) | All 4.6% (2 y) 0 intermediate-risk CNS-IPI 6.2% high-risk CNS-IPI |
| US-MGH, Abramson et al43 | Retrospective | DLBCL High CNS risk† | R-CHOP (97%) | HDMTX 3-3.5 g/m2 (3) | 3%* |
| Australia, Cheah et al44 | Retrospective | DLBCL High CNS risk‡ | 1. CHOP(-like) ± R§ 2. CHOP(-like) ± R 3. Dose-intense | 1. None (IT alone) 2. HDMTX 1-3 g/m2 (2) 3. HDMTX 1-3 g/m2 (2) (+IT) | 1. 18.4% (3 y) 2. 6.9% (3 y) 3. 2.3% (3 y) P = .009 |
| Italy, Ferreri et al45 | Retrospective | DLBCL High CNS risk¶ | R-CHOP | None HDMTX 3 g/m2 ± IT | 12%* 0 |
| Study . | Study type . | Lymphoma type/risk . | Primary treatment . | Systemic CNS prophylaxis (# cycles) . | CNS relapse . |
|---|---|---|---|---|---|
| GELA/LYSA, Tilly et al40 | Prospective phase 3 | All aggressive 80% DLBCL | 1. ACVBP 2. CHOP | 1. HDMTX 3 g/m2 (2) 2. None | 0.8%* 2.7%*P = .002 |
| Nordic, Holte et al41 | Prospective phase 2 | DLBCL (74%) FL 3A aaIPI 2-3 | DI R-CHOEP14 | AraC 3 g/m2 (1) HDMTX 3 g/m2 (1) | 4.4%* |
| UK NCRI/Bloodwise, Phillips et al42 | Prospective phase 2 | DLBCL IPI ≥3 | R-CODOX-M-R-IVAC | HDMTX 3 g/m2 (+IT) Ifosfamide, AraC (+IT) | All 4.6% (2 y) 0 intermediate-risk CNS-IPI 6.2% high-risk CNS-IPI |
| US-MGH, Abramson et al43 | Retrospective | DLBCL High CNS risk† | R-CHOP (97%) | HDMTX 3-3.5 g/m2 (3) | 3%* |
| Australia, Cheah et al44 | Retrospective | DLBCL High CNS risk‡ | 1. CHOP(-like) ± R§ 2. CHOP(-like) ± R 3. Dose-intense | 1. None (IT alone) 2. HDMTX 1-3 g/m2 (2) 3. HDMTX 1-3 g/m2 (2) (+IT) | 1. 18.4% (3 y) 2. 6.9% (3 y) 3. 2.3% (3 y) P = .009 |
| Italy, Ferreri et al45 | Retrospective | DLBCL High CNS risk¶ | R-CHOP | None HDMTX 3 g/m2 ± IT | 12%* 0 |
ACVBP, doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone; CVAD, cyclophosphamide, vincristine, doxorubicin, and dexamethasone; DI, dose intensive; GELA, Groupe d’Etudes des Lymphomes de l’Adulte; LYSA, Lymphoma Study Association; R-CODOX-M-R-IVAC, cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate (CODOX-M)/ifosfamide, etoposide, and high-dose cytarabine (IVAC).
Reported as frequency of CNS relapse.
High CNS risk = 1, high-risk EN sites (bone marrow, sinus, testes, epidural disease, liver, kidney/adrenal/orbit; 2, >2 EN sites and elevated LDH; 3, high risk by Hollender criteria.
High CNS risk = 1, high-risk EN sites (bone marrow, breast, testis, kidney/adrenal, sinus, nasopharynx, liver, paravertebral; 2, any two of the following: multiple EN sites, elevated LDH, or B symptoms.
Three treatment groups are listed: (1) 1991-2003 CHOP(-like) CHOP and MACOP-B (HD-MTX <1 g/m2) with IT MTX; (2) >2003 R-CHOP and HD-MTX (1-3 g/m2) following R-CHOP completion; and (3) <65 y, age-adjusted IPI ≥2, hyper-CVAD or CODOX-M-IVAC ± rituximab (when available), and IT MTX.
High CNS risk = 1, high-risk EN sites (testis, spine, skull, sinus, orbit, nasopharynx, kidney/adrenal, breast); 2, advanced stage and increased LDH.