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. 2025 Apr 24;7(1):vdaf082.
doi: 10.1093/noajnl/vdaf082. eCollection 2025 Jan-Dec.

Primary central nervous system lymphoma: Predictors of response to induction therapy and patterns of progression

Louis Cappelli  1 , Allison Kayne  2 , Jennifer Newman  3 , Ahmed Elguindy  4 , Narendranath Epperla  5 , Joshua D Palmer  4 , Ubaldo Martinez Outschoorn  6 , Pierluigi Porcu  6 , Wenyin Shi  1 , Iyad Alnahhas  7
Affiliations

Primary central nervous system lymphoma: Predictors of response to induction therapy and patterns of progression

Louis Cappelli et al. Neurooncol Adv. .

Abstract

Background: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive variant of non-Hodgkin lymphoma. While PCNSL is often sensitive to induction high-dose methotrexate (HDMTX) based chemotherapy, recurrence rates remain high, approaching 50% within 5 years. The most common molecular alterations in PCNSL include mutations in MYD88 and CD79 and CDKN2A homozygous deletion. There are no predictive or prognostic molecular markers in PCNSL.

Methods: We conducted a retrospective review of 40 patients with PCNSL treated at Thomas Jefferson University and Ohio State University between 2011 and 2023. We created a clinically annotated database of patient characteristics and outcomes. For 13 patients whose paraffin-embedded tissue was available for analysis, Illumina's Infinium Global Diversity Array with Cytogenetics was used to make copy number change calls.

Results: The most commonly used induction chemotherapy regimens were HDMTX monotherapy and HDMTX with rituximab. The overall response rate to induction chemotherapy was 75%. A total of 25% had resistant disease to induction chemotherapy. The median follow-up was 20.3 months. The median progression-free survival for the entire cohort was 30.64 months (range 3.42-57.86 months); 2.56 months for the resistant group and 44.88 months for the sensitive group (P-value < .001). The median overall survival for the entire cohort was 64.8 months (range 41.47-88.13 months); 13.97 months for the resistant group and 81.43 months for the sensitive group (P-value = .046).

Conclusions: The initial response to induction chemotherapy is an important prognostic factor in PCNSL. There is a need for improved predictive biomarkers of response to treatment in PNCLS.

Keywords: CDKN2A; HDMTX; PCNSL; induction chemotherapy; relapse.

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Conflict of interest statement

Louis Cappelli: none declared. Allison Kayne: none declared. Jennifer Newman: none. 243 declared. Ahmed Elguindy: none declared. Narendranath Epperla: none declared. Joshua D. Palmer:. 244 grants from Genetech (Phase II clinical trial in HCRN network, outside submitted work), NIH R702. 245 (Photon vs Proton clinical study, outside submitted work), NIH R01CA269948 (Multi-institutional GBM. 246 imaging Artificial Intelligence study, outside submitted work), payments/honoraria from Varian Medical. 247 Systems, Novocure, and ICOTEC. Ubaldo Martinez Outschoorn: none declared. Pierluigi Porcu: none. 248 declared. Wenyin Shi: consulting fees from BrainLab, Novocure, Zai Lab, and Varian Medical System. Iyad. 249 Alnahhas: none declared.

Figures

Figure 1.
Figure 1.
(A) Local versus distant progression of PCNSL. (A) is an example of local tumor progression on MRI T1-post contrast (left pre-HDMTX; right post-HDMTX). The black borders correlate with the lesion after progression. (B) Local versus distant progression of PCNSL. (B) is an example of distant tumor progression on MRI T1-post contrast (left pre-HDMTX; right post-HDMTX). The black borders correlate with the lesion after progression.
See this image and copyright information in PMC

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