2009 Background: Primary DLBCL of the CNS is a rare extranodal lymphoma confined to the CNS. Despite standard high-dose methotrexate (HD-MTX)-based induction therapy, approximately 25% of patients (pts) relapse after an initial response, and effective salvage options are limited with reported objective response rate (ORR) generally <30% and median progression-free survival (PFS) <3 months. The SPECTRUM trial evaluated efficacy and safety of tislelizumab plus pemetrexed in pts with R/R primary DLBCL of the CNS (NCT05253118). Methods: SPECTRUM is a phase II, multicenter, open-label study conducted in South Korea. Pts with histologically confirmed R/R primary DLBCL of the CNS after HD-MTX-based therapy were eligible. Tislelizumab (200 mg) plus pemetrexed (500 mg/m 2 ) was administered intravenously every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed ORR per IPCG response criteria. Secondary endpoints included PFS, duration of response (DoR), overall survival (OS), and safety. Exploratory analyses assessed baseline CSF and plasma MYD88 L265P mutations using droplet digital PCR and genetic subtypes based on LymphGen classification. Results: As of December 16, 2025, 29 pts were enrolled. Median age was 59 years (range, 41–86), 17 (58.6%) were male, and 25 (86.2%) had prior rituximab exposure. Median follow-up was 30.4 months (95% confidence interval CI, 16.8–not reached NR), with a median of 6 treatment cycles (range, 1–55). Among evaluable pts, the ORR was 71.4% (20/28), with complete response (CR) rate of 50.0% (14/28). Median DoR was 14.5 months (95% CI, 2.8–NR). Median PFS and OS were 6.8 (95% CI, 2.1–27.6) and 27.8 months (95% CI, 7.4–NR), respectively. Treatment-emergent adverse events (TEAEs) of any grade occurred in 19 pts (65.5%), most commonly skin rash (51.7%). Grade ≥3 TEAEs occurred in 10 pts (34.5%), including one grade 5 event. Six pts discontinued treatment due to treatment-related AEs, all attributable to pemetrexed. Immune-related AEs occurred in 5 pts (17.2%). Most pts were MCD subtype (84.6% 22/26), with MYD88 L265P mutations detected in 61.5% (16/26). At baseline, MYD88 L265P detection was higher in CSF than plasma cell-free DNA (cfDNA) (85.0% 17/20 vs 20.0% 4/20). In one pt with extra-CNS relapse harboring MYD88 L265P mutation and PIM1 – CD274 fusion, MYD88 L265P became undetectable at Weeks 6 and 12, concordant with metabolic CR on PET/CT. Conclusions: Tislelizumab plus pemetrexed met the primary endpoint and demonstrated encouraging outcomes (ORR 71.4% CR 50.0%; median PFS and DoR 6.8 and 14.5 months) with manageable safety profiles in pts with R/R primary DLBCL of the CNS. Clinical trial information: NCT05253118 .
Kim et al. (2026) studied this question.