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 brain1,3-5

PCNSL accounts for1,3-5:

2%-3% of all
NHL diagnoses

4% of all
brain tumors

PCNSL is a predominantly diffuse large B-cell lymphoma5,6
  • Located in the brain, spinal cord, leptomeninges, or eyes
  • With no evidence of systemic involvement

In the US7

~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 65 years, and these patients require additional consideration due to8-11:
  • 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 nonspecific12-14

Patients may present with personality changes or symptoms of increased intracranial pressure such as headache, nausea, and vomiting12-14

ct and mri icon

CT and MRI findings may not confirm the diagnosis

brain icon

Stereotactic brain biopsy remains the gold standard for diagnosing PCNSL

Significant delays can occur before diagnosis14:
  • Median of 21 days from onset of symptoms to neuroimaging
  • Up to 14 days from biopsy until diagnosis of PCNSL and start of treatment
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A delay from symptom onset to treatment initiation is strongly correlated with reduced survival14

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 PCNSL2,15

Many patients will either be refractory to initial treatment, often HD-MTX–based chemotherapy, or relapse 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 60%

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 outcomes3
  • Most patients whose disease progresses will not achieve a durable second remission2
  • Most relapses occur within the first 2 years of initial diagnosis16
7.2 months

Median overall survival time from first disease progression to death from any cause3

Outcomes among certain patients have remained largely unchanged for decades due to2,11:
  • 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; CT=computed tomography; FDA=Food and Drug Administration; HD-MTX=high-dose methotrexate; IMiDs=immunomodulatory drugs; mAbs=monoclonal antibodies; MRI=magnetic resonance imaging; R/R PCNSL=relapsing or refractory primary central nervous system lymphoma; WBRT=whole brain radiation therapy.

References: 1. Ahn Y, Ahn HJ, Yoon DH, et al. Primary central nervous system lymphoma: a new prognostic model for patients with diffuse large B-cell histology. Blood Res. 2017;52(4):285-292. doi:10.5045/br.2017.52.4.285 
2. 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 3. 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 4. Lv C, Wang J, Zhou M, Xu J-Y, Chen B, Wan Y. Primary central nervous system lymphoma in the United States, 1975–2017. Ther Adv Hematol. 2022;13:20406207211066166. doi:10.1177/20406207211066166 5. Ferreri AJM. How I treat primary CNS lymphoma. Blood. 2011;118(3):510-522. doi:10.1182/blood-2011-03-321349 6. 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
7. Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015-2019. Neuro Oncol. 2022;24(Suppl 5):v1-v95. doi:10.1093/neuonc/noac202 8. Liu Y, Yao Q, Zhang F. Diagnosis, prognosis and treatment of primary central nervous system lymphoma in the elderly population (review). Int J Oncol. 2021;58(3):371-387. doi:10.3892/ijo.2021.5180 9. Schlegel U. Primary CNS lymphoma. Ther Adv Neurol Disord. 2009;2(2):93-104. doi:10.1177/1756285608101222 10. 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 11. 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
12. Haldorsen IS, Espeland A, Larsen JL, Mella O. Diagnostic delay in primary central nervous system lymphoma. Acta Oncol. 2005;44(7):728-734. doi:10.1080/02841860500256272 13. Grommes C, DeAngelis LM. Primary CNS lymphoma. J Clin Oncol. 2017;35(21):2410-2418. doi:10.1200/JCO.2017.72.7602 14. Hasner MC, van Opijnen MP, van der Meulen M, et al. Diagnostics and treatment delay in primary central nervous system lymphoma: what the neurosurgeon should know. Acta Neurochir (Wien). 2024;166(1):261. doi:10.1007/s00701-024-06138-3 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