Table 3. Prospective clinical trials on PCNSL.
| Reference | Year | Treatment strategies | Number of patients | Median age (years) | Median PFS (months) | Median OS (months) | OR, PR + CR [%] |
|---|---|---|---|---|---|---|---|
| DeAngelis (88) | 1992 | M [1] + RT [40 + 14 boost] + AraC [3] | 31 | 58 | 41 | 42.5 | 27/31 [87] |
| Nelson (44) | 1992 | RT [40 + 20 boost] | 41 | NR | NR | 12.2 | 21/26 [81] |
| Glass (89) | 1994 | M [3.5] + RT [30–40] | 25 | 56 | 32 | 33 | 23/25 [92] |
| Schultz (90) | 1996 | CHOP + RT [41.4 + 18 boost] | 52 | NR | 9.2 | 16.1 | 10/52 [19] |
| O’Neill (91) | 1999 | CHOP + RT [50.4] + AraC | 55 | 60 | 6.7 | 9.7 | 32/53 [60] |
| Mead (92) | 2000 | RT [40 + 14 boost] ± CHOP | 53 | 57 | 10 vs. 22 | NR | NR |
| O’Brien (93) | 2000 | M [1] + RT [45 + 5.4 boost] | 46 | 58 | NR | 33 | 44/46 [96] |
| Abrey (94) | 2000 | M [3.5] + P [100] + V [1.4] + AraC [3] + IT M + IT A + RT [45] | 52 | 65 | NR | 60 | 49/52 [94] |
| Ferreri (95) | 2001 | M [3] + P [100] + V [1.4] + AraC [3] + RT [45] | 13 | 54 | 18 | ≥25 | 12/13 [92] |
| DeAngelis (96) | 2002 | M [2.5] + V [1.4] + P [100] + AraC [3] + IT M + RT [45] | 102 | 56.5 | 24 | 37 | 47/50 [94] |
| Poortmans (97) | 2003 | M [3] + Ten [100] + B [100] + pred [60] + IT M + IT A + RT [40] | 52 | 51 | NR | 46 | 42/52 [81] |
| Abrey (98) | 2003 | M [3.5] + AraC [3]; BEAM | 28 (14 transplanted) | 53 | 5.6 | Not reached | Induction: 16/24 [57], SCT: 11/14 [79] |
| Batchelor (99) | 2003 | M [8] | 25 | 60 | 12.8 | 22.8 | 17/23 [74] |
| Pels (49) | 2003 | M [5] + AraC [3] + V [2] + ifos [800] + dex [10] + cyclo [200] + IT M + IT A + IT P | 65 | 62 | 21 | 50 | 43/61 [71] |
| Herlinger (100) | 2005 | M [8] | 37 | 60 | 10 | 25 | 13/37 [35] |
| Colombat (101) | 2006 | M [3] + B [100] + eto [100] + pred [60]; BEAM + RT [30] | 25 (17 transplanted) | 52 | 40 | Not reached | Induction: 21/25 [84], SCT 16/16 [100] |
| Illerhaus (102) | 2006 | M [8] + AraC [3] + thio [40 mg/m2]; B [400] + thio [5 mg/kg] + RT [45] | 30 (23 transplanted) | 54 | NR | Not reached | Induction: 21/30 [70], SCT 21/21 [100] |
| Ferreri (50) | 2009 | M [3.5] + AraC [2] + RT [45] | 79 | 59; 58 | 3; 18 | NR | 27/39 [69]; 16/40 [40] |
| Thiel (53) | 2010 | M [3; + ifos] + RT [45] | 526 (all); 318 (PPP) | 61 | 18.3; 11.9 | 32.4; 37.1 | 283/526 [54] |
| Morris (103) | 2013 | R [500] + M [3.5] + V [1.4] + P [100] + RT [23.4] | 52 | 60 | 92.4 | Not reached | 41/52 [79] |
| Rubinstein (104) | 2013 | R [375] + M [8] + T [150] + AraC [2] + eto [40] | 44 | 61 | 48 | Not reached | 34/47 [72] |
| Omuro (105) | 2015 | M [3.5] + V [1.4] + P [100] + AraC [3]; M [3.5] + T [150] | 95 | 72; 73 | 9.5; 6.1 | 31; 14 | 37/45 [82]; 34/42 [74] |
| Omuro (106) | 2015 | R [500] + M [3.5] + V [1.4] + P [100]; thio [250] + cyclo [60] + bus [3.2] | 32 (26 transplanted) | 57 | Not reached | Not reached | Induction: 31/32 [97]; SCT 24/26 [92] |
| Ferreri (51) | 2016 | M [3.5] + AraC [2] + R [375] + thio [30] | 227 | 58; 57; 57 | 6; 20; not reached | 12; 30; not reached | 40/75 [53]; 51/69 [74]; 65/75 [87] |
| Glass (107) | 2016 | R [375] + M [3.5] + T [100] + RT [36] | 66 | 57 | 63 | 90 | 30/35 [86] |
| Illerhaus (108) | 2016 | R [375] + M [8] + AraC [3] + thio [40]; R [375] + B [400] + thio [5 mg/kg] | 79 (73 transplanted) | 56 | 74 | Not reached | Induction: 73/79 [92]; SCT: 72/79 [91] |
| Kasenda (109) | 2017 | R [375] + AraC [3] + thio [40]; R [375] + B [400] + thio [5 mg/kg] | 39 (32 transplanted) | 57 | 12.4 | Not reached | Induction: 22/39 [56]; SCT: 22/32 [69] |
| Fritsch (110) | 2017 | R [375] + M [3] + P [60] + L [110] | 107 (all); 69 (R-MPL) | 73 | 10.3 (all); 9.6 (R-MPL) | 20.7 (all); 15.4 (R-MPL) | 53/107 [50]; 32/69 [46% R-MPL] |
| Adhikari (111) | 2018 | AraC [3] + RT [45] | 22 | 51.5 | 11.25 | 19 | 18/22 [82] |
| Rubenstein (79) | 2018 | LEN [10] + R [375]; LEN [15] + R [375]; LEN [20] + R [375] | 14 | 66 | NR | NR | 9/14 [64] |
| Wu (112) | 2018 | FTD: FOT [100] + Ten [60] + dex [40]; HD-MA: M [3.5] + AraC [1] | 49 (FTD: 24, HD-MA: 25) | FTD: 56; HD-MA: 57 | 17.4; 16.7 | 48.8; 44.9 | FTD: 21/24 [88]; HD-MA: 21/25 [84] |
| Tun (113) | 2018 | POM [5] + DEX [40] | 25 | 60 | 9 | 4.7 | 12/25 [48] |
| Ghesquieres (114) | 2019 | LEN [20] + R [375] | 34 | 69 | 7.8 | 17.7 | 12/34 [35] |
| Houillier (52) | 2019 | R [375] + M [3] + AraC [3] + RT [40]; R [375] + M [3] + AraC [3] + ASCT | 140 (70 transplanted) | 47; 53 | NR | NR | 44/70 [63]; 61/70 [87] |
| Ferreri (115) | 2019 | R [375] + CHOP + NGR-hTNF [0.8] | 12 | 61 | NR | NR | 9/12 [75] |
| Soussain (75) | 2019 | IB [560] | 52 | 70 | 4.8 | 19.2 | 27/52 [52] |
| Dietrich (116) | 2020 | PEM [900] | 17 | 63.7 | 4.2 | 44.5 | 12/17 [71] |
| Ferreri (117) | 2020 | R [375] + CHOP + NGR-hTNF [0.8] | 28 | 58 | NR | NR | 21/28 [75] |
| Seidel (118) | 2020 | IT M [3] + AraC [3] | 65 | 62 | NR | 53 | 42/65 [65] |
| Chiesa (119) | 2020 | TMZ [3.5] + RT [30] | 9 | 67 | Not reached | 79 | 6/9 [67] |
| Narita (120) | 2021 | TIR [480] | 44 | 60 | 2.9 | Not reached | 28/44 [64] |
| Fox (121) | 2021 | TIER | 27 | 64 | 3 | 5 | 14/27 [52] |
| Ferreri (122) | 2022 | MA; MATRix; WBRT or ASCT | 219 | 62 | NR | 21% vs. 37% vs. 56% | NR |
A, cytarabine; AraC, cytarabine (g/m2); B, carmustine (mg/m2); BEAM, carmustine, etoposide, cytarabine, melphalan; bus, busulfan (mg/kg); chemo, chemotherapy; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; CR, complete remission; cyclo, cyclophosphamide (mg/m2); dex, dexamethasone; DEX, dexamethasone (mg/day); eto, etoposide (mg/m2); FOT, fotemustine (mg/m2); FTD, fotemustine, teniposide and dexamethasone; HD-MA, high-dose methotrexate plus cytarabine; IB, ibrutinib (mg/day); ifos, ifosfamide (mg/m2); IT A, intrathecal cytarabine; IT M, intrathecal methotrexate; IT P, intrathecal prednisone; L, lomustine (110 mg/m2); LEN, lenalidomide (mg/day); M, methotrexate (g/m2); MA, mitoxantrone, cytarabine; MATRix, methotrexate, cytarabine, thiotepa, and rituximab; NGR-hTNF, tumor necrosis factor-a coupled with NGR (μg/m2); NR, not reported; OR, overall response; OS, overall survival; P, procarbazine (mg/m2/day); PCNSL, primary central nervous system lymphoma; PEM, pemetrexed (mg/m2); PFS, progression-free survival; POM, pomalidomide (mg); PPP, per-protocol population; PR, partial remission; pred, methylprednisolone (mg/m2); R, rituximab (mg/m2); R-MPL, rituximab, methotrexate, procarbazine and lomustine; RT, radiation therapy (dose used in Gy); SCT, stem cell transplant; T, temozolomide (mg/m2); Ten, teniposide (mg/m2); thio, thiotepa (mg/m2); TIER, thiotepa in combination with ifosfamide, etoposide, and rituximab; TIR, tirabrutinib (mg/day); TMZ, temozolomide (g/m2); V, vincristine (mg/m2); WBRT, whole-brain radiotherapy; ASCT, autologous stem cell transplantation.