Patterns of Disease Progression in patients with newly diagnosed Primary Central Nervous System Lymphoma Following Treatment with High-Dose Methotrexate

Abstract Introduction: Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin's lymphoma that primarily affects the brain, spinal cord, and/or eyes. Despite advances in treatment, PCNSL remains a formidable challenge due to its aggressive nature and limited understanding of disease progression. Recurrence of PCNSL within the central nervous system (CNS) is not uncommon, but patterns of intracranial recurrence following induction chemotherapy have not been extensively studied. This study aims to elucidate the patterns of recurrence in PCNSL, providing insight into the disease’s behavior. Methods: Patient charts and diagnostic imaging from those treated for PCNSL from 2 institutions and ≥ 18 years old from the years 2011-2023 were retrospectively reviewed. Relevant data from the charts to identify disease progression, patterns of recurrence, and survival was collected from the patient charts. The pattern of recurrence was reviewed by comparing the initial diagnostic MRI to the recurrence MRI (T1 post-contrast and T2/FLAIR sequences). The pattern of recurrence was classified as either local or distant depending on the anatomical location of the recurrent lesion. Distant recurrences were classified as those separate from the previous enhancing lesion and located outside of the initial T2/FLAIR abnormality appreciated on imaging. Local recurrences were classified as new lesions that overlapped with the primary enhancing lesion/T2/FLAIR abnormality. Results: 29 out of 47 patients met inclusion criteria with PCNSL and progressed through initial definitive treatment with high-dose methotrexate (HDMTX) or HDMTX and rituximab; with only 1 patient receiving initial management with radiation therapy. The median age at time of diagnosis was 73.0 years (range: 44.0-78.0), with 16 (55.2%) patients being male and 13 (44.8%) female. Eighteen of the 29 patients were found to have multifocal disease. 14/29 (48.3%) patients had distant recurrence only, 11/29 (37.9%) had only local recurrence, whereas 4/29 (13.8%) displayed both local and distant recurrence pattern. The median time until disease progression was 7.1 months (range: 1.3-69.0). Twelve of the 29 patients had a complete response (CR) to initial systemic therapy, 7 had a partial response (PR), and 10 patients had disease progression through HDMTX. Of the 18 patients who had multifocal disease at the time of diagnosis, 6 had disease progression through HDMTX, with 5 experiencing PR and only 7 achieved CR. Conclusion: Patterns of disease progression in patients diagnosed with PCNSL are not very well understood. In this retrospective review, we identified that the majority of disease recurrence in patients diagnosed with PCNSL who underwent HDMTX was outside or distant to the primary disease site vs solely local disease progression intracranially (62.1% vs 37.9%). Such findings need to be illustrated in a larger cohort to confirm such patterns; however, this insight raises awareness of the need for further advances in achieving higher and more durable rates of control for this rare disease.