maze of pcnsl treatment options

Understanding R/R PCNSL
In PCNSL, progression is likely and prognosis is poor1,2

What is PCNSL?

What Is Primary Central Nervous System Lymphoma (PCNSL)?

PCNSL is a highly aggressive type of non-Hodgkin lymphoma (NHL) in which the tumor is mostly confined to the brain1,3-7

PCNSL accounts for1,3-7:

2%-4% of all
NHL diagnoses

4% of all
brain tumors

PCNSL is a predominantly diffuse large B-cell lymphoma4,8
  • Located in the brain, spinal cord, leptomeninges, or eyes
  • With no evidence of systemic involvement

In the US9

~0.45 cases

per

100,000 people are diagnosed 
every year

~1,900 people were diagnosed 
with PCNSL in 2023

The median age at diagnosis is 67 years, and these patients require additional consideration due to5,10-12:
  • Higher rates of comorbidities and impaired performance status
  • Reduced ability to tolerate treatment
  • Higher risk of neurotoxicity

Many patients experience delay in diagnosis

Patients with PCNSL may experience difficulty and delay in diagnosis because their symptoms are often nonspecific13-16

Patients may present with personality changes or symptoms of increased intracranial pressure such as headache, nausea, and vomiting13-16

ct and mri icon

MRI and CT scan findings may not confirm the diagnosis

brain icon

Stereotactic brain biopsy remains the gold standard for diagnosing PCNSL

Brain Biopsy

The extent of disease is determined by CE MRI of the brain and spine, and ophthalmologic and CSF evaluation

Significant delays can occur before diagnosis15:
  • Median of 21 days from onset of symptoms to neuroimaging
  • Up to 14 days from biopsy until diagnosis of PCNSL and start of treatment
arrow

A delay from symptom onset to treatment initiation is strongly correlated with reduced survival15

Learn more about the challenges of diagnosing PCNSL from the experts

Resources
Leading experts discuss the challenges of managing R/R PCNSL
Open Modal
Progression & Prognosis

Relapsed and Refractory Disease Is Common in Patients With PCNSL2,17-20

Many patients will either experience disease refractory to guideline-recommended first-line, HD-MTX–based chemotherapy, or relapsed disease after initially responding to treatment. Patients who are refractory may have inherent differences in biology and clinical outcomes compared with those who relapse, which may affect the treatments they receive in later lines.

About 1/3

of patients may be refractory to first-line MTX-based chemotherapy regimens

Up To 45%

of patients may eventually relapse after
response to first-line treatment

Outcomes Are Particularly Poor for Patients With R/R PCNSL

PCNSL is highly likely to progress, leading to poor outcomes21
  • Most patients whose disease progresses will not achieve a durable second remission2
  • Most relapses occur within the first 2 years of initial diagnosis22
6.8 months

Median overall survival time from first disease progression to death from any cause18

Outcomes among certain patients have remained largely unchanged for decades due to2,12:
  • Delay in diagnosis
  • Poor performance status
  • Substantial comorbidities
  • No FDA-approved treatments indicated for R/R PCNSL
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Many patients with R/R PCNSL are not candidates for further intensive therapy2

The R/R PCNSL treatment 
landscape is complex
Current Treatment Challenges

*May include targeted agents, immunomodulatory agents, or other monotherapy/combination regimens.2

Not all drugs within the presented classes are used in the treatment of R/R PCNSL.

ASCT=autologous stem cell transplantation; BTKi=Bruton tyrosine kinase inhibitor; CE=contrast-enhanced; CSF=cerebrospinal fluid; CT=computed tomography; FDA=Food and Drug Administration; HD-MTX=high-dose methotrexate; IMiDs=immunomodulatory drugs; mAbs=monoclonal antibodies; MRI=magnetic resonance imaging; MTX=methotrexate; NHL=non-Hodgkin lymphoma; R/R PCNSL=relapsing or refractory primary central nervous system lymphoma; WBRT=whole brain radiation therapy.

References: 1. Birnbaum T, Bochmann K, von Baumgarten L, Straube A. Early relapses in patients with primary CNS lymphoma treated with methotrexate-based chemotherapy without consolidating whole brain irradiation. J Neurooncol. 2013;112(2):233-239. doi:10.1007/s11060-013-1052-3 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers V.1.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed May 18, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org 3. Ambady P, Doolittle ND, Fox CP. Relapsed and refractory primary CNS lymphoma: treatment approaches in routine practice. Ann Lymphoma. 2021;5:23. doi:10.21037/aol-21-20 4. Tao K, Wang X, Tian X. Relapsed primary central nervous system lymphoma: current advances. Front Oncol. 2021;11:649789. doi:10.3389/fonc.2021.649789 5. Kaulen LD, Baehring JM. Treatment options for recurrent primary CNS lymphoma. Curr Treat Options Oncol. 2022;23(11):1548-1565. doi:10.1007/s11864-022-01016-5 6. Seidel S, Kowalski T, Nilius-Eliliwi V, Schroers R, Schlegel U. Survival, prognostic factors, hospitalization time and clinical performance status after first cerebral relapse or progression in 54 patients with primary CNS lymphoma not eligible for high dose chemotherapy: a retrospective analysis. Neurol Res Pract. 2023;5(1):8. doi:10.1186/s42466-023-00234-y 7. Martinez-Calle N, Isbell LK, Cwynarski K, Schorb E. Treatment of elderly patients with primary CNS lymphoma. Ann Lymphoma. 2021;5(2):1-16. doi:10.21037/aol-20-30 8. Holdhoff M, Mrugala MM, Grommes C, et al. Challenges in the treatment of newly diagnosed and recurrent primary central nervous system lymphoma. J Natl Compr Canc Netw. 2020;18(11):1571-1578. doi:10.6004/jnccn.2020.7667 9. Yamanaka R, Morii K, Sano M, et al. Long-term survivors of primary central nervous system lymphoma. Jpn J Clin Oncol. 2017;47(2):101-107. doi:10.1093/jjco/hyw171 10. FDA approves label update for Kite’s Yescarta® for relapsed/refractory primary central nervous system lymphoma. News release. Gilead Sciences, Inc. February 6, 2026. Accessed April 23, 2026. https://www.gilead.com/news/news-details/2026/fda-approves-label-update-for-kites-yescarta-for-relapsedrefractory-primary-central-nervous-system-lymphoma 11. YESCARTA® (axicabtagene ciloleucel). Prescribing information. Kite Pharma, Inc.; 2026. 12. Pinnix CC, Gunther JR, Dabaja BS, et al. Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma. Blood Adv. 2020;4(13):2871-2883. doi:10.1182/bloodadvances.2020001837 13. Sheikh S, Migliorini D, Lang N. CAR T-based therapies in lymphoma: a review of current practice and perspectives. Biomedicines. 2022;10(8):1960. doi:10.3390/biomedicines10081960 14. Holdhoff M, Wagner-Johnston N, Roschewski M. Systemic approach to recurrent primary CNS lymphoma: perspective on current and emerging treatment strategies. Onco Targets Ther. 2020;13:8323-8335. doi:10.2147/OTT.S192379 15. Langner-Lemercier S, Houillier C, Soussain C, et al. Primary CNS lymphoma at first relapse/progression: characteristics, management, and outcome of 256 patients from the French LOC network. Neuro Oncol. 2016;18(9):1297-1303. doi:10.1093/neuonc/now033 16. Mendez JS, Grommes C. Treatment of primary central nervous system lymphoma: from chemotherapy to small molecules. Am Soc Clin Oncol Educ Book. 2018;38:604-615. doi:10.1200/EDBK_200829