Ibrutinib in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Systematic Review.

Gaurav Nepal,Siddhartha Bhandari,Bikram Prasad Gajurel,Yow Ka Shing,Jonathan Quinonez,Trevine Albert,Riwaj Bhagat,Riwaj Bhagat,Riwaj Bhagat,Mahika Khurana,Rajeev Ojha,Utsav Joshi,Steven Licata,Prasun Pudasainee,Domenica Herrera Bucheli,Samir Ruxmohan,Joel Stien,Juan Fernando Ortiz,Jessica Holly Rehrig

doi:10.3390/neurolint14010009

Abstract

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of Non-Hodgkin Lymphoma (NHL) representing 1–2% of all NHL cases. PCNSL is defined as a lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes. Efforts to treat PCNSL by traditional chemotherapy and radiotherapy have generally been unsuccessful as a significant proportion of patients have frequent relapses or are refractory to treatment. The prognosis of patients with Refractory or Relapsed (R/R) PCNSL is abysmal. The optimal treatment for R/R PCNSL is poorly defined as there are only a limited number of studies in this setting. Several studies have recently shown that ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has promising results in the treatment of R/R PCNSL. However, these are preliminary studies with a limited sample size. In this systematic review, we explored and critically appraised the evidence about the efficacy of the novel agent ibrutinib in treating R/R PCNSL.

Highlights

Primary Central Nervous System Lymphoma (PCNSL) is a rare variant of NHL representing 1–2% of all NHL cases
We explore the evidence about the efficacy of the novel agent ibrutinib to treat Refractory or Relapsed (R/R) PCNSL
The number of R/R PCNSL patients recruited in the included studies ranged from 3–52

Summary

Introduction

PCNSL is a rare variant of NHL representing 1–2% of all NHL cases. PCNSL is defined as a lymphoma that presents in the brain, spinal cord, leptomeninges, or eyes, restricted entirely to the craniospinal axis [1]. Efforts to treat PCNSL with systemic regimes used in DLBCL have generally been unsuccessful. Whole-Brain Radiation Therapy (WBRT) was once the standard of care for PCNSL. Standard chemotherapy for systemic NHL, such as Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP)-based regimens, were ineffective for PCNSL, likely due in part to the low penetration of the blood–brain barrier (BBB) [5]. With the introduction of High-Dose Methotrexate (HD-MTX) in the first-line treatment of PCNSL, survival outcomes have greatly improved. Despite high response rates with initial HD-MTX-based treatment, more than half of the initial responders relapse. The prognosis of Refractory or Relapsed (R/R) PCNSL is grim, and the optimal treatment is poorly elucidated as there have only been a limited number of studies conducted in this setting [7]

Results

Discussion

Conclusion