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Multicenter Study
. 2024 Dec:213:115068.
doi: 10.1016/j.ejca.2024.115068. Epub 2024 Oct 13.

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

Fleur A de Groot  1 , Tim J A Dekker  2 , Jeanette K Doorduijn  3 , Stefan Böhringer  4 , Mirian Brink  5 , Ruben A L de Groen  1 , Lorraine M de Haan  6 , F J Sherida H Woei-A-Jin  7 , Troy Noordenbos  6 , Aniko Sijs-Szabo  1 , Mirjam A Oudshoorn  1 , King H Lam  8 , Arjan Diepstra  9 , Liane C J Te Boome  10 , Valeska Terpstra  11 , Lara H Bohmer  12 , Alina Nicolae  13 , Eduardus F M Posthuma  14 , Lianne Koens  15 , Marc F Durian  16 , Jeroen Stavast  17 , Marjolein W M van der Poel  18 , Myrurgia Abdul Hamid  19 , Wendy B C Stevens  20 , Sjo L M van Rooij  21 , Rimke S Oostvogels  22 , Angelika Mühlebner  23 , Karen J Neelis  24 , Michiel van den Brand  25 , Thomas Tousseyn  26 , Daan Dierickx  27 , Okke de Weerdt  28 , Aart Beeker  29 , Patty M Jansen  6 , Marie José Kersten  30 , Josée M Zijlstra  30 , Martine E D Chamuleau  30 , Hendrik Veelken  1 , Jacoline C E Bromberg  31 , Marcel Nijland  32 , Joost S P Vermaat  33
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Free article
Multicenter Study

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

Fleur A de Groot et al. Eur J Cancer. 2024 Dec.
Free article

Abstract

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/m2/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.

Keywords: Clinical characteristics; Consolidation; High-dose methotrexate; Induction; PCNSL; Polychemotherapy; Survival outcomes.

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Conflict of interest statement

Declaration of Competing Interest JKD: honoraria from Eli Lilly/Loxo. MJK: honoraria from and consulting/advisory role for BMS/Celgene, Kite, a Gilead Company, Miltenyi Biotech, Novartis, Adicet Bio, and Roche; research funding from Kite, Roche, Takeda, and Celgene; and travel support from Kite, Miltenyi Biotech, Novartis, Abbvie and Roche. AD: Millennium Takeda: research funding and advisory board. FJSHWAJ: research funding from Kyowa Kirin, Takeda. DD: honoraria from Takeda, Novartis, Amgen, Atara Biotherapeutics, Incyte and Pierre Fabre; Institutional research grants: Kom op tegen Kanker, Stichting tegen Kanker. TT: holds a Mandate for Fundamental and Translational Research from the ‘Stichting tegen Kanker’ (2019–091) and is a co-founder of the Fund ‘Me To You’ supporting research in lymphoma/leukemia (https://www.kuleuven.be/mecenaat/fondsen/geneeskunde/fonds-me-to-you). MCH: research funding GenMab, Celgene/BMS, Gilead, Advisory AbbVie, Novartis. JMZ: research funding Roche, Gilead, Takeda. JSPV: Secura Bio: Consulting or Advisory Role. MN: Genmab: Consultancy; Takeda: Research Funding; Roche: Research Funding. MWMP: Takeda: Consulting or Advisory Role. All remaining authors have declared no conflicts of interest.

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