Cancer Research and Treatment

Original Article

Chemotherapy-Free Salvage Therapy with Rituximab, Lenalidomide, and Poseltinib in Relapsed or Refractory Primary Central Nervous System Lymphoma: A Multi-center, Phase II Study: Dong Hyun Kim, Sanyeowool An, Hongyul Ahn, Han Song, Ka-Won Kang, Sang Eun Yoon, Seok Jin Kim, Hyo Jung Kim, Youngil Koh, Deok-Hwan Yang, Consortium for Improving Survival of Lymphoma (CISL); Received September 6, 2025 Accepted November 11, 2025 Published online November 12, 2025; DOI: https://doi.org/10.4143/crt.2025.977 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Relapsed or refractory (R/R) primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which salvage chemotherapy has limited efficacy. We conducted an investigator-initiated, single-arm, multicenter phase II trial to evaluate the efficacy and safety of a chemotherapy-free salvage regimen comprising rituximab, lenalidomide, and poseltinib (R2P) in patients with R/R PCNSL.
Materials and Methods
The R2P regimen consisted of two phases: six cycles of induction with rituximab, lenalidomide, and poseltinib, followed by three cycles of consolidation with lenalidomide and poseltinib. The primary endpoints were complete response rate (CRR) and overall response rate (ORR). Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).
Results
A total of 10 patients were enrolled (one withdrew before cycle 1; nine were evaluable for efficacy). The median age was 70 years (range, 53 to 75 years), and all had received methotrexate-based first-line chemotherapy. The ORR was 55.6%, and the CRR was 33.3%. The median PFS was 5.6 months, and the median OS was not reached. Next-generation sequencing was performed in four patients (three responders and one non-responder). CD79B missense mutations were identified in all three responders. A total of 11 adverse events (AEs) were observed in six patients. The most common AE was neutropenia (30.0%). The only grade ≥ 3 AE was a single case of grade 3 neutropenia. No dose modifications were required due to toxicity.
Conclusion
Poseltinib in combination with lenalidomide and rituximab showed activity in patients with R/R PCNSL, warranting further investigation in larger studies.

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Case Report

Long-term Complete Remission of Decitabine-Primed Tandem CD19/CD22 CAR-T Therapy with PD-1 and BTK Inhibitors Maintenance in a Refractory Primary Central Nervous System Lymphoma Patient: Rui Zou, Xiao Zhou, Hailing Liu, Peng Wang, Fan Xia, Liqing Kang, Lei Yu, Depei Wu, Zhengming Jin, Changju Qu; Cancer Res Treat. 2023;55(4):1363-1368. Published online June 14, 2023; DOI: https://doi.org/10.4143/crt.2023.371

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

Citations

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Original Article

Combined Chemotherapy and Radiotherapy for Primary CNS Lymphoma: Jeong Eun Lee, Dae Yong Kim, Yong Chan Ahn, Do Hoon Lim, Seung Jae Huh, Seong Soo Shin, Won Seok Kim, Won Ki Kang, Do Hyun Nam, Jung Il Lee, Jong Hyun Kim; Cancer Res Treat. 2001;33(5):398-403. Published online October 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.5.398

Abstract PDF

PURPOSE
This study was performed in order to evaluate the effectiveness of combined chemotherapy and radiotherapy (RT) in primary central nervous system lymphoma (PCNSL).
MATERIALS AND METHODS
From January 1995 to August 1999, 21 patients with a diagnosis of PCNSL were treated with combined chemotherapy and radiotherapy. Their median age was 47 years with range of 19 to 78 years. Twelve patients were male and nine patients were female. All patients were immunocompetent and they had no evidence of systemic lymphoma. All patients underwent placement of an Ommaya reservoir and recieved a combination regimen using pre-RT systemic and intra-Ommaya methotrexate (MTX), 40 Gy whole-brain RT with a 14.4 Gy boost, and 2 courses of post-RT high-dose cytarabine. The median follow-up period of all patients and survived patients were 22 months and 36 months, respectively.
RESULTS
The median overall survival duration was 21 months and the overall two- and four-year survival rates were 51% and 43%, respectively. Complete response (CR), partial response, stable disease, and progressive disease were achieved in 12, 3, 1, and 5 patients, respectively. All nine patients without CR expired within 1-31 months (median 6 months). Two patients among the patients with CR developed recurrence after 13 and 14 months, respectively. The location of recurrent disease was within the port of radiation boost. Survival was influenced by age, performance status, and CR. There was one episode of MTX neurotoxicity and hepatotoxicity,respectively.
CONCLUSION
Combined chemotherapy and radiotherapy was an effective treatment for PCNSL, and was associated with a minimum toxicity. However, we must pay attention to the recurrence and late toxicity, particularly within two years following treatment.

Citations

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Elevated neutrophil-to-lymphocyte ratio as a prognostic factor in primary central nervous system lymphoma
Ruba Memon, Ruju Talati, Richard Song, Matthew Ordon, Karan S Dixit, Osaama H Khan
Neuro-Oncology Advances.2026;[Epub] CrossRef

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