Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies
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<sup>2</sup>/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.
Authors
- Jeanette K. Doorduijn (ORCID: https://orcid.org/0000-0002-1014-0918)
- Martine E.D. Chamuleau (ORCID: https://orcid.org/0000-0002-0123-9182)
- Karen J. Neelis (ORCID: https://orcid.org/0000-0002-3506-4966)
- Lorraine M. de Haan (ORCID: https://orcid.org/0000-0002-6799-9766)
- Fleur A. de Groot (ORCID: https://orcid.org/0000-0001-9940-2891)
- Jacoline E. C. Bromberg (ORCID: https://orcid.org/0000-0002-3830-7142)
- Eduardus F. M. Posthuma (ORCID: https://orcid.org/0000-0002-0882-2346)
- Troy Noordenbos
- Marcel Nijland (ORCID: https://orcid.org/0000-0002-2740-2873)
- Angelika Mühlebner (ORCID: https://orcid.org/0000-0001-9102-7353)
- Michiel van den Brand (ORCID: https://orcid.org/0000-0001-8871-6254)
- Marc Durian (ORCID: https://orcid.org/0009-0008-8810-5187)
- Anikó Sijs‐Szabó
- Daan Dierickx (ORCID: https://orcid.org/0000-0002-8917-022X)
- Marie José Kersten (ORCID: https://orcid.org/0000-0002-8904-3802)
- Rimke Oostvogels (ORCID: https://orcid.org/0000-0003-3650-4588)
- Wendy B.C. Stevens (ORCID: https://orcid.org/0000-0003-3841-9280)
- Lianne Koens
- Valeska Terpstra
- Tim Dekker (ORCID: https://orcid.org/0000-0001-9663-7476)
- King H. Lam (ORCID: https://orcid.org/0000-0003-3903-1085)
- Mirian Brink (ORCID: https://orcid.org/0000-0002-6014-4810)
- Hendrik Veelken (ORCID: https://orcid.org/0000-0002-9108-3125)
- Patty M. Jansen (ORCID: https://orcid.org/0000-0002-2361-9303)
- Joost S.P. Vermaat (ORCID: https://orcid.org/0000-0002-1628-6256)
- Josée M. Zijlstra (ORCID: https://orcid.org/0000-0003-1074-5922)
- Lara H. Böhmer (ORCID: https://orcid.org/0009-0005-6499-4950)
- Feng Jung Sherida H. Woei-A-Jin (ORCID: https://orcid.org/0000-0001-7840-6156)
- Jeroen Stavast
- Mirjam A. Oudshoorn
- Stefan Böhringer (ORCID: https://orcid.org/0000-0001-9108-9212)
- Arjan Diepstra (ORCID: https://orcid.org/0000-0001-9239-1050)
- Thomas Tousseyn (ORCID: https://orcid.org/0000-0002-0397-1086)
- Ruben A. L. de Groen (ORCID: https://orcid.org/0000-0002-2998-2066)
- Alina Nicolae (ORCID: https://orcid.org/0000-0003-3171-0059)
- Okke de Weerdt
- Sjo L M van Rooij
- L.C.J. te Boome
- Aart Beeker
- Marjolein W.M. van der Poel
- Myrurgia Abdul Hamid
Institutions
- University Medical Center Groningen (NL)
- Radboud University Nijmegen (NL)
- University of Groningen (NL)
- Leiden University Medical Center (NL)
- Erasmus MC (NL)
- Radboud University Medical Center (NL)
- University Medical Center Utrecht (NL)
- Maastricht University (NL)
- Medisch Centrum Haaglanden (NL)
- Reinier de Graaf Hospital (NL)
- St. Antonius Ziekenhuis (NL)
- Netherlands Comprehensive Cancer Organisation (NL)
- Haga Hospital (NL)
- Elisabeth-TweeSteden Ziekenhuis (NL)
- Erasmus MC Cancer Institute (NL)
- Amsterdam University Medical Centers (NL)
- Spaarne Gasthuis (NL)
- KU Leuven (BE)
Publication Details
- Journal
- European Journal of Cancer
- Published
- 2024-10-13
- DOI
- https://doi.org/10.1016/j.ejca.2024.115068
- Citations
- 10
- Primary Topic
- CNS Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 3.69