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

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 character¬istics 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.