TY - JOUR
T1 - Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies
AU - de Groot, Fleur A
AU - Dekker, Tim J A
AU - Doorduijn, Jeanette K
AU - Böhringer, Stefan
AU - Brink, Mirian
AU - de Groen, Ruben A L
AU - de Haan, Lorraine M
AU - Woei-A-Jin, F J Sherida H
AU - Noordenbos, Troy
AU - Sijs-Szabo, Aniko
AU - Oudshoorn, Mirjam A
AU - Lam, King H
AU - Diepstra, Arjan
AU - Te Boome, Liane C J
AU - Terpstra, Valeska
AU - Bohmer, Lara H
AU - Nicolae, Alina
AU - Posthuma, Eduardus F M
AU - Koens, Lianne
AU - Durian, Marc F
AU - Stavast, Jeroen
AU - van der Poel, Marjolein W M
AU - Hamid, Myrurgia Abdul
AU - Stevens, Wendy B C
AU - van Rooij, Sjo L M
AU - Oostvogels, Rimke S
AU - Mühlebner, Angelika
AU - Neelis, Karen J
AU - van den Brand, Michiel
AU - Tousseyn, Thomas
AU - Dierickx, Daan
AU - de Weerdt, Okke
AU - Beeker, Aart
AU - Jansen, Patty M
AU - Kersten, Marie José
AU - Zijlstra, Josée M
AU - Chamuleau, Martine E D
AU - Veelken, Hendrik
AU - Bromberg, Jacoline C E
AU - Nijland, Marcel
AU - Vermaat, Joost S P
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/12
Y1 - 2024/12
N2 - Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m
2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.
AB - Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m
2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.
U2 - 10.1016/j.ejca.2024.115068
DO - 10.1016/j.ejca.2024.115068
M3 - Article
C2 - 39427440
SN - 0959-8049
VL - 213
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 115068
ER -