• The efficacy and safety of the use of Columvi in CNS lymphoma have not been established.
• In the Columvi pivotal clinical trial, patients with a current or past history of CNS lymphoma were excluded.

• There is limited information on the use of Columvi in patients with CNS lymphoma.
• In a small retrospective study in patients with R/R DLBCL confined to the CNS, the interim ORR after 2-3 cycles of Columvi was 75% in the 16 evaluable patients. CSF concentrations of Columvi in patients with CR versus those with no CR at the interim assessment did not significantly differ. Grade 1-2 CRS (28%) and Grade‌‌‌‌‌‌‌‌‌ ≥3 ICANS (11%) were reported. Outcomes were also reported for patients who proceeded to consolidation with CD19-directed CAR-T cell therapy followed by Columvi.
• Case series and single case reports have also described the use of Columvi in patients with CNS lymphoma.

AE=adverse event

ASCT=autologous stem cell transplant

CAR-T=chimeric antigen receptor T-cell

CNS=central nervous system

CR=complete response

CRS=cytokine release syndrome

CSF=cerebrospinal fluid

DLBCL=diffuse large B-cell lymphoma

HIV=human immunodeficiency virus

ICANS=immune effector cells-associated neurotoxicity

IT=intrathecal

LBCL=large B-cell lymphoma

ORR=objective response rate

OS=overall survival

PD=progressive disease

PFS=progression-free survival

PR=partial response

R/R=relapsed/refractory

SD=stable disease

The efficacy and safety of the use of Columvi in CNS lymphoma have not been established. In the Columvi pivotal clinical trial, patients with a current or past history of CNS lymphoma were excluded because the ability of Columvi to penetrate the CNS is unknown.[1,2]

Retrospective studies

Yang et al. conducted a retrospective, real-world study to evaluate Columvi in 18 patients with R/R DLBCL confined to the CNS.[3] Columvi was administered as monotherapy using standard step-up dosing with obinutuzumab pre-treatment. Patients were assessed after 2-3 cycles (interim assessment). Those with at least a PR could continue Columvi or undergo consolidation therapy, followed by Columvi, and those who did not respond could receive salvage therapy, including Columvi. The median follow-up was 12 months.

At the interim assessment, 12 of the 16 evaluable patients responded for an interim ORR of 75% (8 CRs and 4 PRs). Of the four non-responders, 1 (6%) had SD and 3 (19%) had PD.[3] Nine patients received CD19-directed CAR-T cell therapy, including 7 responders (after ASCT in 2); 8 patients then resumed Columvi, including 6 responders who completed a total of 6-12 cycles of Columvi. The best ORR was 75% (9 CRs and 3 PRs); one patient with an interim PR achieved CR after consolidation therapy. The median PFS was 15.4 months, and the median OS was not reached; 1-year PFS and OS rates were 62.5% and 68.8%, respectively. Five deaths occurred, due to rapid PD after 2 cycles of Columvi (n=3) and fatal ICANs following CAR-T consolidation (n=2). Columvi was detected in the CSF of 6 of the 10 patients with evaluable samples, and there were no significant differences in the CSF concentrations when stratified by interim treatment response (CR vs no CR, p=0.91).

Safety was evaluated in the 18 patients who received at least one dose of Columvi.[3] During Columvi induction (n=18), Grade ≥3 hematologic AEs were neutropenia (28%) and thrombocytopenia (6%), and Grade ≥3 non-hematologic AEs were fever (11%) and infection (11%). Grade 1-2 CRS (28%) and Grade ≥3 ICANS (11%) were also reported. During post-consolidation Columvi (n=6), Grade ≥3 AEs were neutropenia (33%), fever (17%), and infection (17%).

Reports of use in CNS lymphoma from retrospective studies

Hsu et al. conducted a retrospective study amongst patients with R/R B‐cell lymphomas who had at least three prior lines of therapy and then received Columvi treatment.[4] Among the four patients who had CNS involvement, no additional neurological toxicities were noted during treatment with Columvi. However, none of these patients experienced a positive response to Columvi; all had rapid systemic progression despite the salvage therapy.

Tong et al. conducted a retrospective real‑world multicenter study in East China, including 28 patients with R/R DLBCL, two of whom had primary CNS lymphoma.[5] Both CNS cases responded to Columvi. Overall ORR was 62.5%, and CR was 25%. CRS occurred in 39.3%, of which two were Grade 3, and one patient developed fatal Grade 4 ICANS.

Case series

Neuman et al. reported a case series of eight patients with primary CNS lymphoma (n=2) or secondary CNS lymphoma, with systemic disease (n=2) or isolated (n=4), who were treated with Columvi.[6] One patient with isolated secondary CNS lymphoma had Burkitt’s lymphoma, and the remaining patients had LBCL. Patients received 1-3 lines of prior therapy and 1-12 cycles of Columvi, as a single agent (n=3) or in combination with systemic or IT chemotherapy (n=5). Seven patients (87.5%) achieved a response (4 CRs and 3 PRs), and one patient died of sepsis prior to response assessment after one cycle of Columvi. The two patients with primary CNS lymphoma received 12 cycles of single-agent Columvi and achieved CR. Columvi was detected in CSF samples from 4 out of 5 patients assessed. CRS occurred in three patients (Grade 2, n=1; Grade 1, n=2).

Peng and Tang retrospectively reviewed four cases of patients with CD20 and CD79-positive CNS DLBCL, three with primary CNS lymphoma and one with secondary CNS lymphoma, who received Columvi in combination with lenalidomide.[7] Columvi was administered using standard step-up dosing with obinutuzumab pretreatment. All four patients achieved a response, which included two unconfirmed CRs and two PRs after two treatment cycles, and two CRs, one unconfirmed CR, and one PR after four treatment cycles. Three patients experienced Grade 1 (n=2) or Grade 2 (n=1) CRS and ICANS, one patient experienced Grade 1 CRS, and two patients experienced Grade 1 (n=1) or Grade 2 (n=1) myelosuppression.

Godfrey et al. reported a case series of four CD20-positive R/R DLBCL patients with secondary CNS involvement treated with Columvi.[8] Patients received a median number of 6.5 (range 2-8) cycles of Columvi, using standard step-up dosing. Two patients received obinutuzumab pre-treatment, while two patients did not due to rapidly progressing disease.

Columvi was detected in the CSF of all four patients in concentrations that were sufficient to drive T cell activation and cytotoxicity against CD20-positive lymphoma cells ex vivo.[8] In one patient who had lymphoma involving the CSF, the on-treatment CSF sample showed more than a 12-fold increase in the number of CSF leukocytes and a substantial relative decrease in lymphoma cells compared to the pre-treatment sample, which suggested that Columvi robustly redirected immune cells to the tumour site in this patient. Although three patients showed radiographic and clinical improvement, the contribution of Columvi to the patients’ clinical response could not be definitively assessed due to the low number of patients and the use of concomitant therapies in some cases.

The authors concluded that Columvi partially penetrates the blood-brain barrier and can induce clinical and radiographic responses in patients with CNS lymphoma.[8] As the average CSF concentration of Columvi was only 0.1-0.4% of that in the peripheral blood, these data indicate that only low levels of Columvi are needed in the CSF to elicit responses in CNS lymphoma.

Single case reports

Case reports describing the use of Columvi in patients with CNS lymphoma, including primary CNS lymphoma [9], Richter‑transformed DLBCL isolated to the CNS [10], CNS relapse of mantle cell lymphoma [11], Burkitt lymphoma with CNS involvement [12], and HIV-associated DLBCL with leptomeningeal [13] or CNS [14] involvement, have been reported in the literature.

1. EU RISK MANAGEMENT PLAN FOR COLUMVI/GLOFITAMAB. RMP Version 5.0. 21Feb2025. Accessed June 11, 2026. https://www.ema.europa.eu/en/documents/rmp/columvi-epar-risk-management-plan_en.pdf
2. Hoffmann-La Roche. A Dose Escalation Study of Glofitamab (RO7082859) as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-treatment Dose of Obinutuzumab in Participants With Relapsed/Refractory B-cell Non-hodgkin’s Lymphoma. Accessed April 13, 2024. https://www.clinicaltrials.gov/study/NCT03075696
3. Yang A, Dong J, Deng X, et al. Multicenter Real-World Analysis of Glofitamab in Relapsed/Refractory Primary CNS Lymphoma: Clinical Activity, CNS Penetration, and ctDNA Dynamics. Am J Hematol. 2026;101(7):1763-1775. doi:10.1002/ajh.70342
4. Hsu YT, Wu SJ, Kao HW, et al. Glofitamab as a salvage treatment for B-cell lymphomas in the real world: A multicenter study in Taiwan. Cancer. 2024;130(11):1972-1981. doi:10.1002/cncr.35217
5. Tong J, Jiang S, Luo Q, et al. Real-World Study of Glofitamab for the Treatment of Relapse or Refractory Diffuse Large B-Cell Lymphoma in East China. Blood. 2024;144(Supplement 1):7762. doi:10.1182/blood-2024-204522
6. Neumann MAC, Schneider J, Szameitat M, et al. Glofitamab crosses the blood-brain barrier and exhibits activity against primary and secondary CNS lymphoma. Blood Adv. 2026;10(9):3128-3132. doi:10.1182/bloodadvances.2025019322
7. Peng YY, Tang XQ. Relapsed or refractory central nervous system lymphoma successfully treated by glofitamab combined with lenalidomide. Front Oncol. 2025;15:1685271. doi:10.3389/fonc.2025.1685271
8. Godfrey JK, Gao L, Shouse G, et al. Glofitamab stimulates immune cell infiltration of CNS tumors and induces clinical responses in secondary CNS lymphoma. Blood. 2024;144(4):457-461. doi:10.1182/blood.2024024168
9. Wang W, Chen M, Li J, et al. Glofitamab induces deep and rapid response in relapsed primary central nervous system lymphoma. Leuk Lymphoma. 2025;66(8):1475-1480. doi:10.1080/10428194.2025.2484365
10. Lu K, Chen P, Zhang X, et al. Glofitamab treatment of Richter transformation with isolated central nervous system involvement: a case report. Front Immunol. 2025;16:1635589. doi:10.3389/fimmu.2025.1635589
11. Heini AD, Bacher U, Porret N, et al. Experiences with Glofitamab Administration following CAR T Therapy in Patients with Relapsed Mantle Cell Lymphoma. Cells. 2022;11(17):2747. doi:10.3390/cells11172747
12. Huang Y, Jiang J, Lu J, et al. Case Report: Glofitamab in the treatment of a patient with central nervous system-involved Burkitt lymphoma. Front Oncol. 2026;16:1724213. doi:10.3389/fonc.2026.1724213
13. Tinajero J, Markary T, Ngo D, Kambhampati Thiruvengadam S, Ayyappan S, Mei M. Glofitamab in patients with HIV-associated B-cell lymphoma. Leuk Lymphoma. 2025;66(5):969-972. doi:10.1080/10428194.2024.2444470
14. Ji Y, Gao J, Wei T, Hao M, Qin W. Case report of two patients with refractory HIV-related B-cell lymphoma treated with the monoclonal antibody glofitamab for secondary central nervous system involvement. Front Oncol. 2026;15:1699475. doi:10.3389/fonc.2025.1699475