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152 Consolidation Improves Survival in Primary Central Nervous System Lymphoma without Preference for Type of High-Dose Methotrexate-Based Induction Treatment Regimen

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Treatment of CNS Lymphoma, Neurologic Toxicities, and Relapsed/Refractory DLBCL
Hematology Disease Topics & Pathways:
Research, Clinical Research, Therapies
Saturday, December 10, 2022: 12:15 PM

Fleur A De Groot1*, Jeanette K. Doorduijn, MD, PhD2, Mirian Brink, PhD3*, Ruben A.L. De Groen1*, Lorraine M. De Haan4*, Troy Noordenbos4*, Aniko Sijs-Szabo1*, King Hong Lam, MD, PhD5*, Arjan Diepstra, M.D., Ph.D.6, Liane te Boome7, Valeska Terpstra8*, Lara H. Böhmer, MD9*, Josée M. Zijlstra, MD PhD10, Lianne Koens11*, Marc Durian, MD12*, Mirjam A. Oudshoorn1*, Hendrik Veelken, MD, PhD 1, Marjolein W.M. Van Der Poel13, Myrurgia Abdul Hamid14*, Wendy B.C. Stevens, MD15*, J L.M van Rooij16*, Rimke Oostvogels, MD PhD17*, Karen J. Neelis, MD18*, Michiel van den Brand, MD19*, F.J. Sherida H. Woei-a-Jin, MD MSc20*, Thomas Tousseyn21*, Daan Dierickx, MD22*, Patty M. Jansen4*, Marie Jose Kersten, MD, PhD23,24, Jacoline Bromberg, MD25*, Marcel Nijland, MD, PhD26* and Joost S.P. Vermaat, MD, PhD1

1Department of Hematology, Leiden University Medical Center, Leiden, Netherlands
2Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands
3Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands, Utrecht, Netherlands
4Department of Pathology, Leiden University Medical Center, Leiden, Netherlands
5Erasmus MC, Rotterdam, NLD
6Department of Pathology and Medical Biology, University of Groningen, Groningen, Netherlands
7Department of Hematology, Haaglanden Medisch Centrum, Den Haag, Netherlands
8Pathology, Haaglanden MC, Den Haag, Netherlands
9Department of Hematology, Haga Teaching Hospital, The Hague, Netherlands
10Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands, Amsterdam, Netherlands
11Department of Pathology, Amsterdam UMC, AMC, Amsterdam, Netherlands
12Department of Hematology, St Elisabeth Hospital, Tilburg, Netherlands
13Maastricht University Medical Center, Maastricht, Netherlands
14Maastricht University, Urmond, NLD
15dept hematology, Radboud UMC, Nijmegen, Netherlands
16Neurology, University Medical Center Utrecht, Utrecht, Netherlands
17Department of Hematology, University Medical Center Utrecht, Utrecht, Netherlands
18Department of Radiotherapy, Leiden University Medical Center, Leiden, Netherlands
19Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands
20Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
21Department of Pathology, UZ Leuven, Leuven, Belgium
22University Hospitals Leuven, Leuven, Belgium
23Department of Hematology, Academic Medical Center, Amsterdam, Noord Holland, Netherlands
24Lymphoma and Myeloma Center Amsterdam-LYMMCARE, Amsterdam, Netherlands
25dept of Neuro-Oncology, Daniel den Hoed Cancer Ctr., Rotterdam, Netherlands
26University Medical Center Groningen, Groningen, Netherlands


Primary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin lymphoma with a median overall survival (OS) of 3 years. The current treatment strategies of PCNSL are governed by high-dose methotrexate (HD-MTX)-based (immuno)chemotherapies, and in young and fit patients combined with high-dose cytarabine (HD-AraC). These (immuno)polychemotherapies are preferably consolidated with whole brain radiotherapy (WBRT) or autologous stem cell transplantation (autoSCT). The aim of this large, retrospective multicenter study was to evaluate the outcome of PCNSL patients treated with several HD-MTX-based (immuno)polychemotherapeutic induction regimens with and without consolidation.


A total of 250 consecutive, newly diagnosed PCNSL patients between 2008 and 2021 from 11 Dutch and Belgian hospitals were included. All patients were treated with ≥1 cycle of HD-MTX ≥3g/m2 per cycle, with an intended cumulative dose of ≥12g/m2. HD-AraC was defined as 2g/m2 per cycle with an intended cumulative dose of ≥8g/m2. Patients treated with three different standard first-line regimens with intended cumulative doses of ≥12g/m2 HD-MTX and ≥8g/m2 HD-AraC were allocated to the ‘intense’ treatment group (Figure 1). Patients receiving two other combination regimens of HD-MTX (intended ≥12g/m2) with procarbazine or teniposide and carmustine as standard first-line therapeutic strategy were assigned to the ‘moderate’ treatment group. WBRT with a cumulative dose of 40 Gy and autoSCT (from 2012 onward) were evaluated as sequential consolidation if received within 8 weeks after good response to (immuno)polychemotherapy. Primary end points were best objective response rate (ORR) at any time and 5-year OS.


Of the 250 patients, 142 (57%) were male and the median age at diagnosis was 67 years (range 28-86). In total, 113 (45%) received ‘intense’ treatment and 137 (55%) ‘moderate’ treatment. Considering ORR, 122 patients achieved complete response (CR, 49%), 88 partial response (PR, 35%), 29 stable/progressive disease (SD/PD, 12%) and 11 unknown response (4%).
During follow-up, 117 (47%) patients experienced progression or relapse and 119 (48%) patients died, of which 97 (82%) were lymphoma-related deaths. Median PFS and OS were 2.4 and 3.5 years, respectively. No significant OS difference was found between the ‘intense’ and ‘moderate’ treatment regimens (OS p=0.14) or between any of the HD-MTX-based (immuno)polychemotherapeutic treatment regimens (Figure 1, p=0.54).

In total, 83 (33%) patients received subsequent consolidation therapy of whom 52 (63%) WBRT and 31 (37%) autoSCT. No OS differences between WBRT and autoSCT were observed (Figure 2, p=0.67). Patients receiving consolidation demonstrated a superior OS (p<0.0001) and a significantly better best ORR (p<0.01) compared to unconsolidated patients. All baseline characteristics were comparable between the consolidated and unconsolidated group, except for age (p<0.01) which was higher in the unconsolidated group. To correct for immortal time bias for the consolidation group, landmark (LM) analyses were performed. The significant effect of consolidation was confirmed at LM 5 months (OS p=0.03) and LM 9 months (OS p=0.03) whereas 80% and 98% of the cohort received consolidation, respectively. To evaluate possible confounders, multivariable analysis was performed and confirmed that older age (HR 1.03, CI 1.01-1.05), WHO performance status ≥2 (HR 1.84, CI 1.31-2.57) and elevated LDH (HR 1.78, CI 1.18-2.69) at diagnosis (all p<0.01) have an adverse effect on risk of mortality and consolidation significantly reduced the risk of mortality (HR 0.44, CI 0.30-0.64), in contrast to treatment intensity (HR 0.96, CI 0.67-1.37).


This multicenter study evaluated several first-line HD-MTX-based regimens in a large cohort of PCNSL patients. Sequential consolidation with WBRT or autoSCT was significantly associated with improved OS, regardless of type of HD-MTX-based induction regimens. Disregarding assessment of toxicity, these results together with other studies call for induction therapy with HD-MTX-based (immuno)polychemotherapy irrespective of type of regimen and sequential consolidation therapy with either WBRT or autoSCT, thereby shaping next treatment algorithms.

Disclosures: Doorduijn: Eli Lilly/Loxo: Honoraria, Membership on an entity's Board of Directors or advisory committees. Diepstra: Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Woei-a-Jin: Kyowa Kirin: Research Funding; Takeda: Research Funding. Tousseyn: EUSA Pharma: Consultancy, Speakers Bureau. Dierickx: Novartis: Honoraria; Incyte: Honoraria; Amgen: Honoraria; Roche: Research Funding; Atara Biotherapeutics: Honoraria; Takeda: Consultancy, Honoraria. Kersten: BMS/Celgene: Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Miltenyi Biotech: Honoraria; Novartis: Honoraria; Roche: Honoraria, Research Funding; Takeda: Honoraria; Adicet Bio: Honoraria. Nijland: Takeda: Research Funding; Roche: Research Funding; Genmab: Consultancy.

*signifies non-member of ASH