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, Tim J A Dekker, Jeanette K Doorduijn, Stefan Böhringer, Mirian Brink, Ruben A L de Groen, Lorraine M de Haan, F J Sherida H Woei-A-Jin, Troy Noordenbos, Aniko Sijs-Szabo, Mirjam A Oudshoorn, King H Lam, Arjan Diepstra, Liane C J Te Boome, Valeska Terpstra, Lara H Bohmer, Alina Nicolae, Eduardus F M Posthuma, Lianne Koens, Marc F DurianJeroen Stavast, Marjolein W M van der Poel, Myrurgia Abdul Hamid, Wendy B C Stevens, Sjo L M van Rooij, Rimke S Oostvogels, Angelika Mühlebner, Karen J Neelis, Michiel van den Brand, Thomas Tousseyn, Daan Dierickx, Okke de Weerdt, Aart Beeker, Patty M Jansen, Marie José Kersten, Josée M Zijlstra, Martine E D Chamuleau, Hendrik Veelken, Jacoline C E Bromberg, Marcel Nijland, Joost S P Vermaat*

*Corresponding author for this work

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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/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.

Original languageEnglish
Article number115068
Number of pages9
JournalEuropean Journal of Cancer
Volume213
Early online date13 Oct 2024
DOIs
Publication statusPublished - Dec 2024

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