Cancer Research and Treatment

A Phase II Study of Bendamustine Plus Rituximab in Patients with Relapsed or Progressive Marginal Zone Lymphoma: KCSG LY14-09: Jeong-Ok Lee, Jinny Park, Hye Jin Kang, Shin Young Hyun, Gyeong-Won Lee, Ho-Young Yhim, Hyo Jung Kim, Jong Seok Lee, Dae Seog Heo, Tae Min Kim; Received August 1, 2025 Accepted December 2, 2025 Published online December 3, 2025; DOI: https://doi.org/10.4143/crt.2025.815 [Accepted]

Abstract PDF: Purpose
This multicenter, phase II study examined the efficacy and safety of bendamustine plus rituximab in patients with relapsed or progressive marginal zone lymphoma (MZL).
Materials and Methods
Patients received six cycles of bendamustine 90 mg/m² intravenously on days 2 and 3, rituximab 375 mg/m² intravenously in cycle 1, and 1,400 mg subcutaneously in cycles 2–8 on day 1 every 4 weeks. Bendamustine dose reduction to 60 mg/m² (level -1) and 40 mg/m² (level -2) was allowed based on prespecified toxicity criteria. The primary endpoint was overall response rate (ORR) and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
Results
Among the 26 evaluable patients, 81.8% achieved an ORR, while 40.7% had a complete response. The median PFS was 46.06 months, and the estimated 3-year OS rate was 92.3%. Hematological toxicities, primarily neutropenia (grade 3/4, 48.1%), were the most common adverse events, resulting in both reduction and interruption of bendamustine doses, accounting for 18 (75%) of 24 dose-reduced cycles and 7 (41%) of 17 missed cycles, respectively. Nonhematologic toxicities were generally mild, with nausea and fatigue identified as the most frequently reported toxicities. The mean relative dose intensities were 76.9% (range, 31.5–100) for bendamustine and 91.3% (range, 72.7–100) for rituximab.
Conclusion
Bendamustine plus rituximab is a highly effective and tolerable treatment for patients with relapsed or progressive MZL, providing durable disease control.

110 View
7 Download

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 [Accepted]

Abstract PDF: 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, 53–75), 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.

513 View
70 Download

Impact of Cell-of-Origin and MYC/BCL2 Status on the Risk of Central Nervous System Relapse in Primary Breast Diffuse Large B-Cell Lymphoma: Chang-Hoon Lee, Ga-Young Song, Ho-Young Yhim, Dok Hyun Yoon, Kyu Yun Jang, Sang Eun Yoon, Jin Seok Kim, Jeong-Ok Lee, Hyeon-Seok Eom, Hyewon Lee, Kyoung Ha Kim, Ka-Won Kang, Young Rok Do, Soon Il Lee, Han Sang Lee, Hyo Jung Kim, Ae Ri Ahn, Deok-Hwan Yang, Won Seog Kim, Jae-Yong Kwak; Received August 5, 2025 Accepted November 3, 2025 Published online November 5, 2025; DOI: https://doi.org/10.4143/crt.2025.836 [Accepted]

Abstract PDF: Purpose
Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare entity with a distinct relapse pattern involving the central nervous system (CNS). However, data regarding predictors of CNS relapse in this population remain limited.
Materials and Methods
CNS relapse was retrospectively analyzed in two multicenter cohorts comprising 53 patients with newly diagnosed primary breast DLBCL, including a prospective trial and real-world cohort, all treated with rituximab-based immunochemotherapy. The impact of baseline clinical parameters, cell-of-origin, and MYC/BCL2 dual expression (DE) status on CNS relapse was assessed using a multivariate Cox regression model, separately conducted for the overall study set (n=53) and the immunohistochemical study set (n=36).
Results
By the CNS-International Prognostic Index (CNS-IPI), most patients were classified as low or intermediate risk; no patients were classified as high risk. With a median follow-up of 58.8 months, the 4-year risk of CNS relapse was 15.6% in the overall study set and 14.2% in the immunohistochemical set. MYC/BCL2 DE was identified in 14 patients (38.9%) and was significantly associated with increased risk of CNS relapse (4-year risk, 30.7% vs. 0%, p=0.001). Patients with non-germinal center B-cell–like subtype had a numerically higher risk of CNS relapse. However, in multivariate analysis, only MYC/BCL2 DE status was associated with CNS relapse. Synchronous bilateral involvement was also an independent predictor of CNS relapse in both study sets. CNS-IPI was not discriminatory for CNS relapse.
Conclusion
MYC/BCL2 DE and synchronous bilateral breast involvement may help identify patients at higher risk for CNS relapse. Further studies are warranted.

383 View
42 Download

Effectiveness of CAR-T Cell Therapies for Relapsed/Refractory Follicular Lymphoma: An External Control Arm Study: Hee-Jin Seo, Ju Hwan Kim, Sang Eun Yoon, Won Seog Kim, Dong Keon Yon, Ju-Young Shin, Seok Jin Kim; Received December 10, 2024 Accepted September 15, 2025 Published online September 17, 2025; DOI: https://doi.org/10.4143/crt.2024.1181 [Accepted]

Abstract PDF: Purpose
Axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabactagene maraleucel (liso-cel) have received regulatory approval for relapsed or refractory follicular lymphoma (r/r FL). However, the data are scare on their comparative effectiveness against the salvage therapies available in real-world settings. This study aimed to indirectly compare treatment outcomes of axi-cel, tisa-cel, and liso-cel versus usual care in South Korean patients with FL.
Materials and Methods
To assess effectiveness in real-world data, aggregate data from the ZUMA-5, ELARA, and TRANSCEND FL studies were compared with individual patient data from the Samsung Medical Center – Lymphoma Cohort Study (SMC-LCS). Patients meeting ZUMA-5, ELARA, and TRANSCEND FL eligibility criteria were selected as the external control arm. All eligible treatment lines per patient were analyzed as independent episodes and weighted using the matching-adjusted indirect comparison (MAIC) method. Time-to-event outcomes were assessed with weighted Kaplan-Meier analysis, and adjusted hazard ratios (aHR) were estimated using Cox proportional hazards models.
Results
Axi-cel included 127 patients, tisa-cel included 94, liso-cel included 101, and 121 episodes from 49 patients were analyzed in the external control arm. The weighted hazard ratios for overall survival (OS) and progression-free survival (PFS) for axi-cel versus the external control were 0.37 (95% CI, 0.21-0.64), 0.35 (95% CI, 0.20-0.59), respectively. For tisa-cel, the HRs were 0.24 (95% CI, 0.11-0.53), and 0.35 (95% CI, 0.20-0.60), respectively. For liso-cel, the HRs were 0.38 (95% CI, 0.13-1.04), and 0.36 (95% CI, 0.15-0.88), respectively.
Conclusion
All three CAR-T therapies showed outstanding effectiveness compared to conventional treatments in usual care in South Korea.

807 View
102 Download

Prognostic Role of SOCS1 Mutations in Diffuse Large B-Cell Lymphoma: Xin-Yi Zhang, Tong-Yao Xing, Wei Hua, Yue Li, Yi-Lin Kong, Bi-Hui Pan, Xin-Yu Zhang, Jia-Zhu Wu, Hao-Rui Shen, Hua Yin, Li Wang, Jian-Yong Li, Rui Gao, Jin-Hua Liang, Wei Xu; Received April 14, 2025 Accepted August 29, 2025 Published online September 1, 2025; DOI: https://doi.org/10.4143/crt.2025.420 [Accepted]

Abstract PDF: Purpose
This study investigates the prognostic impact of SOCS1 mutations in diffuse large B-cell lymphoma (DLBCL) and explores the underlying biological mechanisms, focusing on immune regulation and cellular metabolism.
Materials and Methods
We included 2,590 DLBCL patients from 7 publicly databases (integrated cohort) and 202 additional DLBCL cases from our institution (JSPH cohort). Next-generation sequencing (NGS) was used to detect SOCS1 mutations in DLBCL patients. We analyzed the association between these mutations and overall survival (OS) and progression-free survival (PFS). Additionally, we examined how SOCS1 mutations might influence immune responses, cellular metabolism, and signaling pathways, particularly in the ST2 subtypes of DLBCL.
Results
In the integrated cohort, 15.1% of patients carried SOCS1 mutations, with 12.3% of these mutations located in the SOCS-BOX domain. SOCS1 mutations were found to be more frequent in the GCB and ST2 subtypes of DLBCL. In the integrated cohort, patients with SOCS1 mutations had significantly better OS (p=0.015) and PFS (p=0.007). Mutations located in the SOCS-BOX domain were associated with even better OS (p=0.015) and PFS (p=0.012). In the JSPH cohort, transcriptomic analyses indicated enhanced interferon signaling, immune activation, and downregulation of metabolic pathways in SOCS1-mut cases, especially within the ST2 subtype. These alterations may contribute to a more favorable tumor microenvironment and improved clinical outcomes.
Conclusion
SOCS1 mutations, particularly those in the SOCS-BOX domain, are associated with improved prognosis in DLBCL. By promoting immune activation and inhibiting cellular metabolism, these mutations may not only serve as prognostic biomarkers but also provide insights into potential therapeutic avenues.

624 View
35 Download

Clinicopathological Significance of Tumor-Infiltrating T Lymphocytes and Macrophages in Primary Large B-Cell Lymphoma of Immune-Privileged Sites: Jinseong Kim, Deokhoon Kim, Hyungwoo Cho, Dok-Hyun Yoon, Heounjeong Go; Received June 19, 2025 Accepted August 12, 2025 Published online August 13, 2025; DOI: https://doi.org/10.4143/crt.2025.641 [Accepted]

Abstract PDF

Purpose
Immune-privileged large B-cell lymphomas (IP-LBCLs), comprising primary central nervous system lymphoma (PCNS-LBCL), primary vitreoretinal lymphoma (PVR-LBCL), and primary testicular lymphoma (PT-LBCL), originate in sites with limited immune surveillance. Owing to their rarity, the prognostic implications of the tumor microenvironment in IP-LBCLs remain unclear, warranting further investigation.
Materials and Methods
This study evaluated 109 IP-LBCL cases (PCNS-LBCL, n=87; PT-LBCL, n=22; six cases of PVR-LBCL excluded) using multiplex immunohistochemistry on tissue microarrays, along with clinicopathological analysis. Immune cell infiltration, tumor major histocompatibility complex (MHC) class I, and programmed death ligand-1 (PD-L1) expression, and their associations with clinical outcomes, were evaluated.
Results
PT-LBCL demonstrated higher infiltration of all tumor-infiltrating T lymphocyte (TIL) subsets than PCNS-LBCL (all p<0.05). Elevated CD4⁺ and CD8⁺ T-cell levels correlated with prolonged progression-free survival (PFS) (both p<0.05). M1 macrophage infiltration was associated with improved PFS (p=0.005) and independently predicted a favorable prognosis (hazard ratio = 0.49, p=0.041). Loss of MHC class I expression was more frequent in PT-LBCL than in PCNS-LBCL (77.3% vs. 9.2%; p<0.001). TIL infiltration predicted improved PFS only when the tumor MHC class I was preserved. Moreover, programmed death protein-1 (PD-1)⁺ TILs and tumor PD-L1 expression were associated with prognosis in conjunction with various clinicopathological variables.
Conclusion
These findings highlight the favorable prognostic role of TILs and M1 macrophages, and underscore the complex immune–tumor interactions in IP-LBCLs, despite their origin in immune-privileged sites.

Citations

Citations to this article as recorded by

The Landscape of Primary Central Nervous System Lymphoma (PCNSL): Clinicopathologic and Genomic Characteristics and Therapeutic Perspectives
Huijuan Jiang, Lin Nong
Cancers.2025; 17(17): 2909. CrossRef

813 View
45 Download
1 Crossref

BTG1 Mutation Correlates with Inferior Prognosis in Diffuse Large B-Cell Lymphoma: Chun-Yu Shang, Wei Hua, Tong-Yao Xing, Kai-Xin Du, Yi-fan Wu, Yue Li, Hua Yin, Hao-Rui Shen, Li Wang, Jian-Yong Li, Rui Gao, Wei Xu, Jin-Hua Liang; Received May 8, 2025 Accepted July 30, 2025 Published online July 30, 2025; DOI: https://doi.org/10.4143/crt.2025.494 [Accepted]

Abstract PDF: Purpose
B celltranslocation gene 1 (BTG1) is a highly conserved gene and recurrently mutated in the MCD subtype of diffuse large B-cell lymphoma (DLBCL). The speciﬁc enrichment of BTG1 mutation (BTG1^mut) raises a potential hypothesis that they may actively contribute to DLBCL. However, the biological characteristics and prognostic significance of BTG1 in DLBCL remain to be explored. Therefore, the objective of our study was to evaluate the value of BTG1 in DLBCL.
Materials and Methods
The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Tumor tissue samples of DLBCL patients diagnosed in Jiangsu Province Hospital (JSPH) from 2021 to 2023 were collected for NGS, 195 samples were analyzed the gene expression levels using RNA-seq, among them, 40 samples were analyzed by untargeted metabolomic.
Results
We enrolled 2,379 DLBCL patients from 5 published studies and 243 DLBCL patients from Jiangsu Province Hospital (JSPH) cohort. 11.0% (262/2379) of patients were BTG1^mut in external cohort, compared with 25.1% (61/243) in the JSPH cohort. BTG1^mut was associated with adverse clinical features and was prone to involve testis. Patients with BTG1^mut exhibit inferior overall survival (OS). Furthermore, pathway enrichment analysis of the untargeted metabolomic showed that several meaningful pathways have been found such as amino acid metabolism and lipid metabolism.
Conclusion
BTG1 mutation was promising prognostic predictor for DLBCL. The mechanism driving different survival outcomes may be attributed to the tumor metabolic reprogramming.

817 View
57 Download

Pancreatic Irradiation Dose as a Risk Factor for Elevation in Hemoglobin A1c Level and Diabetes Mellitus in Patients with Indolent Gastroduodenal Lymphoma: Jong Yun Baek, Do Hoon Lim, Dongryul Oh, Jae J Kim, Jun Haeng Lee, Byung-Hoon Min, Hyuk Lee; Received June 2, 2025 Accepted July 28, 2025 Published online July 29, 2025; DOI: https://doi.org/10.4143/crt.2025.585 [Accepted]

Abstract PDF: Purpose
This study investigated the association between pancreatic irradiation dose and HbA1c elevation in patients with indolent gastroduodenal lymphomas treated with radiotherapy (RT). Material and Methods We retrospectively reviewed 103 patients treated at Samsung Medical Center between 2010 and 2023, with or without RT. Patients were stratified by mean pancreas dose (<2300 cGy vs. ≥2300 cGy). The primary outcome was the 2-year HbA1c elevation, with additional time-to-event analyses for HbA1c elevation ≥0.5% and diabetes mellitus (DM) development.
Results
RT was administered to 62 (60.2%) patients, while 41 (39.8%) did not receive RT. There was no significant difference in baseline characteristics except for cancer type. Patients with a mean pancreas dose ≥2300 cGy had a significantly greater 2-year HbA1c increase than those receiving <2300 cGy (p=0.003) or no RT (p<0.001). No significant difference was found between patients receiving <2300 cGy and those without RT (p=0.120). In multivariate time-to-event analysis, a mean pancreas dose ≥2300 cGy was the sole significant risk factor for an HbA1c increase ≥0.5% (p<0.001), while mean pancreas dose <2300 cGy did not show a significant effect (p=0.851). Furthermore, a mean pancreas dose ≥2300 cGy (p=0.017) and baseline prediabetes (HbA1c ≥5.7%) (p=0.023) were independent predictors of DM development.
Conclusion
A mean pancreas dose ≥2300 cGy was associated with HbA1c elevation, whereas doses <2300 had minimal effect. Given the established link between higher HbA1c level and increased risk of DM and cardiovascular events, pancreatic dose reduction should be considered in RT planning for patients with an expected good prognosis.

639 View
22 Download

A Novel CD58 Mutation-Related Signature Predicts Prognosis Risk in Diffuse Large B-Cell Lymphoma Patients: Hui-Li Wang, Chun-Yu Shang, Wei Hua, Hua Yin, Yue Li, Jun-Heng Liang, Rui Gao, Bi-Hui Pan, Xin-Yu Zhang, Jia-Zhu Wu, Hao-Rui Shen, Li Wang, Jian-Yong Li, Jin-Hua Liang, Wei Xu; Received November 27, 2024 Accepted July 21, 2025 Published online July 28, 2025; DOI: https://doi.org/10.4143/crt.2024.1143 [Accepted]

Abstract PDF

Purpose
CD58, a ligand of the CD2 receptor on T cells and NK cells, is abnormally expressed in diffuse large B-cell lymphoma (DLBCL). However, data on the value of CD58 mutation (CD58mut) in DLBCL are limited. Here, we aimed to evaluate the characteristics and prognostic value of CD58^mut in DLBCL patients
Materials and Methods
The available clinical information and corresponding mutation data of DLBCL were obtained from published articles. Ultimately, 3025 DLBCL patients in published cohorts were enrolled in the final analysis. Among the 202 DLBCL patients in the Jiangsu Province Hospital (JSPH) cohort, all tumor tissue samples were collected to perform NGS and gene expression were analyzed via RNA-seq.
Results
We found that 8.2% (250/3025) of patients were CD58^mut in integrated cohort, whereas 11.3% (23/202) in JSPH cohort. CD58^mut patients exhibit inferior progression-free survival (PFS) (the integrated cohort: HR=0.96,95% CI:0.77–1.20, p=0.663 the JSPH cohort: HR=1.85,95% CI:0.85–4.04, p=0.052) and overall survival (OS) (the integrated cohort: HR=1.43,95% CI:1.15-1.77, p<0.001; the JSPH cohort: HR=2.40,95% CI:0.83–6.93, p=0.026). A model based on six signature genes (MRO, OXTR, RASL11A, RLN1, SIGLEC1 and PROM2) was constructed via machine learning. To optimize risk stratification and survival prediction for CD58^mut patients, biological mechanism of the poorer prognosis in high-risk group may be related to the greater abundance of immunosuppressive cells, especially M2 macrophages.
Conclusion
Our results indicated that CD58^mut could serve as a novel prognostic factor for DLBCL patients, and further exploration of personalized treatment strategies for high-risk DLBCL patients based on the risk score model is needed.

Citations

Citations to this article as recorded by

ESAE-SDA: ensemble sparse autoencoder framework for epigenomics-informed snoRNA-disease associations prediction
Xinqing Jiang, Xiaojun Chen, Lifeng Xu, Feng Zhang, Jiawei Chen, Wenqian Zhang
BMC Bioinformatics.2025;[Epub] CrossRef

933 View
57 Download
1 Crossref

Comparative Effectiveness of Anbalcabtagene Autoleucel versus Tisagenlecleucel in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma: Hee-Jin Seo, Woo Hyeon Yoo, Kyungyeon Jung, Ji Won Kim, Ju-Young Shin, Ju Hwan Kim, Won Seog Kim; Received March 10, 2025 Accepted July 10, 2025 Published online July 11, 2025; DOI: https://doi.org/10.4143/crt.2025.276 [Accepted]

Abstract PDF: Purpose
Anbalcabtagene autoleucel (anbal-cel) is a second-generation CD19-targeted chimeric antigen receptor-T cell therapy reducing T-cell exhaustion through PD-1 and TIGIT downregulation. We compared efficacy of anbal-cel with tisagenlecleucel (tisa-cel) in relapsed/refractory diffuse large B-cell lymphoma using external control arm study design.
Materials and Methods
We performed a matching-adjusted indirect comparison (MAIC) using individual patient data from CRC01-01 (NCT#04836507) and aggregate data from JULIET trial (NCT#02445248). Primary outcomes were overall survival (OS) and progression free-survival (PFS), with corresponding hazard ratio (HR) and 95% confidence interval (CI) assessed using weighted Cox proportional hazard model. Secondary outcomes were objective response rate (ORR) and complete response rate (CRR), with corresponding odds ratio (OR) and 95% CI assessed using weighted logistic regression model.
Results
We included 79 patients in CRC01-01 and 115 in JULIET trial. In naïve comparison, median OS was not reached (NR; 95% CI 13.1-NE) for anbal-cel versus 11.1 months (6.6-23.9) for tisa-cel, corresponding to HR of 0.54 (0.34-0.87). Median PFS was 5.5 months (4.2-16.2) versus 2.9 months (2.3-5.2) with HR of 0.73 (0.50-1.08). ORR was 73.4% versus 53.0% with OR of 2.45 (1.32-4.54), and CRR was 64.6% versus 39.1% with OR of 2.83 (1.56-5.13). After applying MAIC to balance prognostic factors between the groups, adjusted HRs or ORs were 0.47 (0.23-0.95) for OS, 0.59 (0.36-0.96) for PFS, 2.60 (1.04-6.52) for ORR, and 3.00 (1.30-6.92) for CRR.
Conclusion
Anbal-cel showed superior effectiveness over tisa-cel, with higher response rates and improved survival outcomes, even after accounting for imbalances in prognostic factors at trial enrollment.

825 View
74 Download

Detection of HIV RNA after CAR-T Cell Therapy in A Relapsed/refractory Diffuse Large B-cell Lymphoma Patient: Possibility of False Positivity and Clinical Implications: Sang Eun Yoon, Kyungmin Huh, Tae Yeul Kim, Hee Jae Huh, Seok Jin Kim, Won Seog Kim; Received May 8, 2025 Accepted June 26, 2025 Published online June 30, 2025; DOI: https://doi.org/10.4143/crt.2025.491 [Accepted]

Abstract PDF: CAR-T cell therapy using lentiviral vectors can lead to false-positive HIV RNA detection, making distinguishing true infection from vector-related signals challenging. A 64-year-old male with relapsed/refractory DLBCL (RR-DLBCL) underwent multiple lines of treatment, including R-CHOP, R-ICE, autologous stem cell transplantation (ASCT), and tisagenlecleucel (tisa-cel, Kymriah). Infectious disease screening before CAR-T therapy was negative for HIV. However, four months post-infusion, during evaluation for second-line CAR-T therapy targeted CD20, HIV RNA was detected in Roche Cobas HIV-1 assay targeted dual target, 5'LTR and gag gene (48 copies/mL). Serial testing showed persistent but low-level positivity of HIV RNA. Retrospective analysis of stored serum samples revealed HIV RNA negativity before tisa-cel infusion but positivity post-infusion in Roche Cobas HIV-1 assay. Additional testing using the Alinity m HIV-1 assay (dual target: 5'LTR and pol gene) and the Abbott RealTime HIV-1 assay (single-target: pol gene) confirmed that only the dual-target assay yielded positive results, suggesting lentiviral vector cross-reactivity rather than actual HIV infection. This case underscores the potential for false-positive HIV-1 RNA detection in CAR-T cell treatment recipients due to vector-derived sequences, emphasizing the need for cautious interpretation of HIV-1 testing.

1,062 View
77 Download

Advances in T-Cell–Directed Immunotherapy for Adult Mature B-Cell Lymphoma: A Comprehensive Review of CAR T-Cell and Bispecific Antibody Therapies: Jinchul Kim, Seok Jin Kim; Cancer Res Treat. 2025;57(4):905-922. Published online June 26, 2025; DOI: https://doi.org/10.4143/crt.2025.440

Abstract PDF PubReader ePub: B-cell lymphomas are a heterogeneous group of malignancies with a high relapse rate after conventional therapies. T-cell–mediated immunotherapies, notably chimeric antigen receptor (CAR) T-cell therapies and T-cell–engaging bispecific antibodies (BsAbs), have transformed treatment paradigms by harnessing the immune system to target malignant cells. This review analyzes the efficacy and safety profiles of several CD19-targeted CAR T-cell therapies and emerging CD20×CD3 BsAbs across various B-cell lymphoma subtypes. While these therapies have demonstrated high response rates and potential for durable remissions, challenges such as cytokine release syndrome, neurotoxicity, and infections remain significant. Understanding these mechanisms and managing adverse effects are crucial for optimizing clinical outcomes and guiding future research in personalized treatment strategies.

2,426 View
166 Download

Clinical Relevance of Starting Alectinib at a Reduced Dose in Patients with ALK-Positive Non–Small Cell Lung Cancer: Junkyu Kim, Min-Ji Kim, Jinyong Kim, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Received December 14, 2024 Accepted April 22, 2025 Published online April 24, 2025; DOI: https://doi.org/10.4143/crt.2024.1209 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
Alectinib has been approved for anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) at 300 mg twice daily in Japan, lower than global standard of 600 mg twice daily. This study evaluated the clinical relevance of the reduced dose by comparing outcomes between the two doses.
Materials and Methods
This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared.
Results
Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg twice daily, respectively. The 300 mg group showed a slight but not significant advantage in PFS (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.44 to 1.51; p=0.51) and overall survival (HR, 0.51; 95% CI, 0.20 to 1.21; p=0.13). Superior outcome with 300 mg was remarkable in patients with lower body weight (≤ 60 kg), but diminished in patients with higher body weights. Patients with baseline brain metastasis in the 300 mg group exhibited a slight increase in incidence of CNS failure (HR, 1.76; 95% CI, 0.53 to 5.8; p=0.36). Although the safety profiles were mostly mild, adverse events were more frequent in the 600 mg group, 50% of which requiring dose reduction.
Conclusion
Alectinib at 300 mg twice daily seems an acceptable dose in East Asians with ALK-positive NSCLC. Notably, our data favor 300 mg twice daily in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.

991 View
88 Download

Hematologic malignancy

Long-term Clinical Efficacy of Radiotherapy for Patients with Stage I-II Gastric Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue: A Retrospective Multi-institutional Study: Jae Uk Jeong, Hyo Chun Lee, Jin Ho Song, Keun Yong Eom, Jin Hee Kim, Yoo Kang Kwak, Woo Chul Kim, Sun Young Lee, Jin Hwa Choi, Kang Kyu Lee, Jong Hoon Lee; Cancer Res Treat. 2025;57(2):570-579. Published online October 4, 2024; DOI: https://doi.org/10.4143/crt.2024.651

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to evaluate long-term treatment outcomes in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma treated with radiotherapy (RT).
Materials and Methods
A total of 229 patients who received RT in 10 tertiary hospitals between 2010 and 2019 were included in this multicenter analysis. Response after RT was based on esophagogastroduodenoscopy after RT. Locoregional relapse-free survival (LRFS) and disease-free survival (DFS), and overall survival (OS) were evaluated.
Results
After a median follow-up time of 93.2 months, 5-year LRFS, DFS, and OS rates were 92.8%, 90.4%, and 96.1%, respectively. LRFS, DFS, and OS rates at 10 years were 90.3%, 87.7%, and 92.8%, respectively. Of 229 patients, 228 patients (99.6%) achieved complete remission after RT. Five-year LRFS was significantly lower in patients with stage IIE than in those with stage IE (77.4% vs. 94.2%, p=0.047). Patients with age ≥ 60 had significantly lower LRFS than patients with age < 60 (89.3% vs. 95.1%, p=0.003). In the multivariate analysis, old age (≥ 60 years) was a poor prognostic factor for LRFS (hazard ratio, 3.72; confidence interval, 1.38 to 10.03; p=0.009). Grade 2 or higher gastritis was reported in 69 patients (30.1%). Secondary malignancies including gastric adenocarcinoma, malignant lymphoma, lung cancer, breast cancer, and prostate cancer were observed in 11 patients (4.8%) after RT.
Conclusion
Patients treated with RT for localized gastric MALT lymphoma showed favorable 10-year outcomes. Radiation therapy is an effective treatment without an increased risk of secondary cancer. The toxicity for RT to the stomach is not high.

Citations

Citations to this article as recorded by

Dosimetric evaluation of cone beam computed tomography-guided online adaptive radiotherapy in gastric mucosa-associated lymphoid tissue lymphoma
Masanori Takaki, Taka-aki Hirose, Tadamasa Yoshitake, Keiji Matsumoto, Yuko Shirakawa, Hiroaki Wakiyama, Osamu Hisano, Hikaru Imafuku, Kousei Ishigami
Technical Innovations & Patient Support in Radiation Oncology.2025; 35: 100321. CrossRef
Gastrointestinal Lymphomas: A Comprehensive Review of Epidemiology, Clinical Features, Diagnosis, Histopathology, and Management
Vignesh Krishnan Nagesh, Ruchi Bhuju, Ahmed S. Mohammed, Emelyn Martinez, Marina Basta, Deepa Francis, Shraboni Dey, Maggie James, Damien Islek, Sanket Bhattarai, Mohammed A. Saafan, Shruthi Badam, Adam Atoot
Lymphatics.2025; 3(4): 31. CrossRef

3,346 View
130 Download
1 Web of Science
2 Crossref

Higher Microbial Abundance and Diversity in Bronchus-Associated Lymphoid Tissue Lymphomas Than in Non-cancerous Lung Tissues: Jung Heon Kim, Jae Sik Kim, Noorie Choi, Jiwon Koh, Yoon Kyung Jeon, Ji Hyun Chang, Eung Soo Hwang, Il Han Kim; Cancer Res Treat. 2025;57(2):580-589. Published online September 30, 2024; DOI: https://doi.org/10.4143/crt.2024.689

Abstract PDF Supplementary Material PubReader ePub

Purpose
It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method.
Materials and Methods
DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed.
Results
Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues.
Conclusion
This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

Citations

Citations to this article as recorded by

Microbial infection and treatment strategies in cancer patients
Kejing Zhu, Zhibo Yuan, Jingli Li, Ailing Fu
Frontiers in Microbiology.2025;[Epub] CrossRef

2,670 View
133 Download
1 Web of Science
1 Crossref

Clinical Impact of Microbiome Characteristics in Treatment-Naïve Extranodal NK/T-Cell Lymphoma Patients: Sang Eun Yoon, Woorim Kang, Junhun Cho, Mauricio Chalita, Je Hee Lee, Dong-Wook Hyun, Hyun Kim, Seok Jin Kim, Won Seog Kim; Cancer Res Treat. 2025;57(2):597-611. Published online August 16, 2024; DOI: https://doi.org/10.4143/crt.2024.675

Abstract PDF Supplementary Material PubReader ePub: Purpose
Extranodal natural killer/T-cell lymphoma (ENKTL) predominantly manifests in East Asia and Latin America. Despite shared intrinsic factors, such as ethnic and genetic backgrounds, the progression of ENKTL can be influenced by extrinsic factors related to changing lifestyle patterns.
Materials and Methods
This study collected stool samples from newly diagnosed (ND)–ENKTL patients (n=40) and conducted whole genome shotgun sequencing.
Results
ND-ENKTL revealed reduced alpha diversity in ND-ENKTL compared to healthy controls (HCs) (p=0.008), with Enterobacteriaceae abundance significantly contributing to the beta diversity difference between ENKTL and HCs (p < 0.001). Functional analysis indicated upregulated aerobic metabolism and degradation of aromatic compounds in ND-ENKTL. Enterobacteriaceae were associated not only with clinical data explaining disease status (serum C-reactive protein, stage, prognosis index of natural killer cell lymphoma [PINK], and PINK-E) but also with clinical outcomes (early relapse and short progression-free survival). The relative abundance of Enterobacteriaceae at the family level was similar between ENKTL and diffuse large B-cell lymphoma (DLBCL) (p=0.140). However, the ENKTL exhibited a higher abundance of Escherichia, in contrast to the prevalence of Enterobacter and Citrobacter in DLBCL. Linear regression analysis demonstrated a significant association between Escherichia abundance and programmed cell death-ligand-1 (PD-L1) levels in tissue samples (p=0.025), whereas no correlation with PD-L1 was observed for Enterobacteriaceae at the family level (p=0.571).
Conclusion
ND-ENKTL exhibited an abundance of Enterobacteriaceae and a dominant presence of Escherichia. These microbial characteristics correlated with disease status, treatment outcomes, and PD-L1 expression, suggesting the potential of the ENKTL microbiome as a biomarker and cause of lymphomagenesis, which warrants further exploration.

2,708 View
131 Download

Nivolumab in Relapsed or Refractory Primary Central Nervous System Lymphoma: Multicenter, Retrospective Study: Jun Ho Yi, Seok Jin Kim, Sang-A Kim, Jongheon Jung, Dok Hyun Yoon; Cancer Res Treat. 2025;57(2):590-596. Published online August 16, 2024; DOI: https://doi.org/10.4143/crt.2024.531

Abstract PDF PubReader ePub

Purpose
Given that 40%-50% of primary central nervous system lymphoma (PCNSL) tissues exhibit aberrancy on 9p24.1, immune checkpoint inhibitors (ICI) may work for the disease.
Materials and Methods
To define the role of ICIs in PCNSL, we carried out a nationwide retrospect analysis for 22 patients who had been treated with nivolumab monotherapy for relapsed or refractory PCNSL.
Results
The median age at diagnosis was 66, and male: female ratio was 1:1. Patients received nivolumab after a median of 3 lines (range, 2 to 6) of therapy and at the median age of 67 years (range, 37 to 82 years). Eleven patients (50%) were refractory to the last treatment prior to nivolumab. With a median follow-up duration of 22.3 months (95% confidence interval [CI], 13.1 to 31.5), nine patients (41%) had an objective response (6 complete responses, 3 partial responses), and the median duration of response was 20.9 months (95% CI, 1.7 to 40.0). The median progression-free survival and overall survival were 2.1 months (95% CI, 0.2 to 4.0) and 18.9 months (95% CI, 5.0 to 32.8), respectively. Nivolumab was generally well-tolerated as no patients required dose reduction and only two patients required delay of treatment.
Conclusion
Our study suggests that nivolumab can be a reasonable option with the durable response for RR PCNSL.

Citations

Citations to this article as recorded by

Targeting PD-L1 for PCNS-DLBCL: from molecular effects to clinical translation
Jiajia Cao, Shuzhen Xiong, Shuni Zhang, Ningning Yue, Chongyang Wu
Frontiers in Immunology.2025;[Epub] CrossRef
Relapsed or refractory central nervous system lymphoma successfully treated by glofitamab combined with lenalidomide
Yin-yin Peng, Xiao-qiong Tang
Frontiers in Oncology.2025;[Epub] CrossRef
Immunotherapy in central nervous system tumors
Yutao Huang, Yi Liu, Hui Zeng, JingJing Yang, Zongping Li, Jianguo Xu, Liyuan Jin, Xiaoyin Liu, Liangxue Zhou
International Journal of Surgery.2025; 111(11): 8301. CrossRef

2,739 View
149 Download
3 Web of Science
3 Crossref

Assessing the Efficacy of Bortezomib and Dexamethasone for Induction and Maintenance Therapy in Relapsed/Refractory Cutaneous T-Cell Lymphoma: A Phase II CISL1701/BIC Study: Yoon Seok Choi, Joonho Shim, Ka-Won Kang, Sang Eun Yoon, Jun Sik Hong, Sung Nam Lim, Ho-Young Yhim, Jung Hye Kwon, Gyeong-Won Lee, Deok-Hwan Yang, Sung Yong Oh, Ho-Jin Shin, Hyeon-Seok Eom, Dok Hyun Yoon, Hong Ghi Lee, Seong Hyun Jeong, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2025;57(1):267-279. Published online July 16, 2024; DOI: https://doi.org/10.4143/crt.2024.479

Abstract PDF Supplementary Material PubReader ePub

Purpose
This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea.
Materials and Methods
Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response.
Results
Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression.
Conclusion
This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Citations

Citations to this article as recorded by

Influence of Hypoxia on Tumor Heterogeneity, DNA Repair, and Cancer Therapy: From Molecular Insights to Therapeutic Strategies
Dominika Kunachowicz, Paulina Tomecka, Mikołaj Sędzik, Jarosław Kalinin, Jacek Kuźnicki, Nina Rembiałkowska
Cells.2025; 14(14): 1057. CrossRef

3,849 View
184 Download
1 Web of Science
1 Crossref

Pediatric cancer

The Effect of Hematopoietic Stem Cell Transplantation on Treatment Outcome in Children with Acute Lymphoblastic Leukemia: Hee Young Ju, Na Hee Lee, Eun Sang Yi, Young Bae Choi, So Jin Kim, Ju Kyung Hyun, Hee Won Cho, Jae Kyung Lee, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo; Cancer Res Treat. 2025;57(1):240-249. Published online July 5, 2024; DOI: https://doi.org/10.4143/crt.2024.155

Abstract PDF PubReader ePub: Purpose
Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups.
Materials and Methods
A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease.
Results
Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment.
Conclusion
HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

5,393 View
182 Download

Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study: Tingting Chen, Chenggong Zeng, Juan Wang, Feifei Sun, Junting Huang, Jia Zhu, Suying Lu, Ning Liao, Xiaohong Zhang, Zaisheng Chen, Xiuli Yuan, Zhen Yang, Haixia Guo, Liangchun Yang, Chuan Wen, Wenlin Zhang, Yang Li, Xuequn Luo, Zelin Wu, Lihua Yang, Riyang Liu, Mincui Zheng, Xiangling He, Xiaofei Sun, Zijun Zhen; Cancer Res Treat. 2024;56(4):1252-1261. Published online May 28, 2024; DOI: https://doi.org/10.4143/crt.2024.104

Abstract PDF Supplementary Material PubReader ePub

Purpose
The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored.
Materials and Methods
On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL).
Results
A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse.
Conclusion
This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Citations

Citations to this article as recorded by

Advances and updates in pediatric anaplastic large cell lymphoma
Lianna J. Marks, Eric Lowe, Kala Kamdar
Blood Advances.2025; 9(19): 4870. CrossRef

4,058 View
151 Download
1 Web of Science
1 Crossref

Head and Neck cancer

The Impact of Infectious Mononucleosis History on the Risk of Developing Lymphoma and Nasopharyngeal Carcinoma: A Retrospective Large-Scale Cohort Study Using National Health Insurance Data in South Korea: So Hee Kang, Yun-Hee Lee, Jun-Pyo Myong, Minsu Kwon; Cancer Res Treat. 2024;56(4):1077-1083. Published online April 23, 2024; DOI: https://doi.org/10.4143/crt.2023.1356

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to assess the long-term risks associated with a history of infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV). Specifically analyzing the potential increase in developing nasopharyngeal cancer (NPC) and lymphoma in patients with a history of IM and exploring the prevalence of other EBV-associated conditions.
Materials and Methods
The Korean National Health Insurance Service (NHIS) database was utilized for a retrospective analysis, covering data from 2002 to 2021. A total of 25,582 IM patients and controls were included, with 1:1 propensity score matching. The study monitored outcomes, including lymphoma, NPC, gastric cancer, multiple sclerosis, and all-cause mortality.
Results
Patients with a history of IM demonstrated a significantly higher incidence of lymphoma (hazard ratio [HR], 5.320; 95% confidence interval [CI], 3.208 to 8.820; p < 0.001) and NPC (HR, 7.116; 95% CI, 1.617 to 31.314; p=0.009) during the follow-up period compared with the control group. Additionally, the IM group showed an increased rate of all-cause mortality (HR, 2.225; 95% CI, 1.858 to 2.663; p < 0.001).
Conclusion
This study suggests that individuals with a history of IM have an elevated risk of developing lymphoma and NPC in South Korea, emphasizing the importance of vigilant follow-up and monitoring. The results advocate for heightened awareness and potential national monitoring policies to address the long-term health implications of EBV infection and to implement preventive measures.

Citations

Citations to this article as recorded by

Epstein-Barr virus (EBV) infection and its sequelae in the immunocompetent host
Madeline R. Meirhaeghe, Henry H. Balfour
Journal of Clinical Virology.2025; 180: 105854. CrossRef

4,971 View
148 Download
1 Web of Science
1 Crossref

Hematologic malignancy

Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma: Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2024;56(3):920-935. Published online January 16, 2024; DOI: https://doi.org/10.4143/crt.2023.869

Abstract PDF Supplementary Material PubReader ePub

Purpose
The feasibility of sequencing circulating tumor DNA (ctDNA) in plasma as a biomarker to predict early relapse or poor prognosis in patients with follicular lymphoma (FL) receiving systemic immunochemotherapy is not clear.
Materials and Methods
We sequenced DNA from cell-free plasma that was serially obtained from newly diagnosed FL patients undergoing systemic immunochemotherapy. The mutation profiles of ctDNA at the time of diagnosis and at response evaluation and relapse and/or progression were compared with clinical course and treatment outcomes.
Results
Forty samples from patients receiving rituximab-containing immunochemotherapy were analyzed. Baseline sequencing detected mutations in all cases, with the major detected mutations being KMT2C (50%), CREBBP (45%), and KMT2D (45%). The concentration of ctDNA and tumor mutation burden showed a significant association with survival outcome. In particular, the presence of mutations in CREBBP and TP53 showed poor prognosis compared with patients without them. Longitudinal analysis of ctDNA using serially collected plasma samples showed an association between persistence or reappearance of ctDNA mutations and disease relapse or progression.
Conclusion
Analysis of ctDNA mutations in plasma at diagnosis might help predict outcome of disease, while analysis during follow-up may help to monitor disease status of patients with advanced FL. However, the feasibility of ctDNA measurement must be improved in order for it to become an appropriate and clinically relevant test in FL patients.

Citations

Citations to this article as recorded by

Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Circulating tumor DNA in lymphoma: technologies and applications
Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal of Hematology & Oncology.2025;[Epub] CrossRef
Molecular pathology of lymphoma and its treatment strategies: from mechanistic elucidation to precision medicine
Zhongyu Wang, Shuai Feng, Xiangmei Yao, Renbin Zhao, Yujin Li, Maofeng Zheng, Zengzheng Li, Yajie Wang
Frontiers in Immunology.2025;[Epub] CrossRef
Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment
Alexis Claudel, Anne-Ségolène Cottereau, Emmanuel Bachy, Emmanuel Itti, Pierre Feugier, Cedric Rossi, Francois Lemonnier, Vincent Camus, Nicolas Daguindau, Guillaume Cartron, Emmanuelle Nicolas-Virelizier, Diana-Laure Mboumba, Christophe Cardoso, Côme Bom
Blood.2025; 146(8): 913. CrossRef
Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL
Chengqian Chen, Wei Guo, Haotian Wang, Luming Cao, Ou Bai
Frontiers in Immunology.2025;[Epub] CrossRef
Genetic analysis of cell-free DNA in follicular lymphoma in comparison with tissue-derived DNA
Yoshikazu Hori, Hiroki Hosoi, Mitsuo Osuga, Ryuta Iwamoto, Fumiyo Maekawa, Tadashi Okamura, Shogo Murata, Toshiki Mushino, Motomi Osato, Hitoshi Ohno, Nobuyuki Yamamoto, Shin-Ichi Murata, Yasuhiro Koh, Sonoki Takashi
Leukemia & Lymphoma.2025; : 1. CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review
Marie Hairing Enemark, Jonas Klejs Hemmingsen, Maja Lund Jensen, Robert Kridel, Maja Ludvigsen
International Journal of Molecular Sciences.2024; 25(20): 11179. CrossRef

5,343 View
183 Download
7 Web of Science
8 Crossref

Assessment of Bone Marrow Involvement in Extranodal NK/T-Cell Lymphoma: Positron Emission Tomography versus Bone Marrow Biopsy, and the Significance of Minimal Involvement by EBV+ Cells (KROG 18-09): Tae Hoon Lee, Hyun Ju Kim, Jong Hoon Lee, Jeongshim Lee, Jin Hee Kim, Dongryul Oh, Keun-Yong Eom; Cancer Res Treat. 2024;56(2):688-696. Published online December 11, 2023; DOI: https://doi.org/10.4143/crt.2023.1049

Abstract PDF PubReader ePub

Purpose
This study aims to investigate the diagnostic significance of positron emission tomography/computed tomography (PET/CT) in assessing bone marrow (BM) involvement through a comparison of PET/CT findings with BM biopsy in extranodal natural killer/T-cell lymphoma.
Materials and Methods
The medical records of 193 patients were retrospectively reviewed. Patients were categorized as having early-stage (PET-ES) or advanced-stage (PET-AS) disease based on PET/CT results. The BM involvement was classified into three groups according to BM biopsy: gross BM involvement, minimal BM involvement (defined as the presence of a limited number of Epstein-Barr virus–positive cells in BM), and no involvement. Calculations of the accuracy of PET/CT in detecting BM involvement and analysis of the clinical outcomes (progression-free survival [PFS] and overall survival [OS]) according to the BM biopsy status were performed.
Results
PET/CT exhibited a sensitivity of 64.7% and a specificity of 96.0% in detecting gross BM involvement. For detecting any (both gross and minimal) BM involvement, the sensitivity was 30.4%, while the specificity was 99.0%. Only one patient (0.7%) demonstrated gross BM involvement among the PET-ES group. Survival outcomes of the PET-ES group with minimal BM involvement (3-year PFS, 55.6%; OS, 77.0%) were closer to those of the PET-ES group with no BM involvement (3-year PFS, 62.2%; OS, 80.6%) than to those of the PET-AS group (3-year PFS, 20.1%; OS, 29.9%).
Conclusion
PET/CT exhibits high specificity, but moderate and low sensitivity in detecting gross and minimal BM involvement, respectively. The clinical significance of minimal BM involvement for patients in the PET-ES group may be limited.

Citations

Citations to this article as recorded by

Magnetic Resonance Imaging and [18F]‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography‐Guided Therapy Improves Survival in Upper Aerodigestive Tract NK/T‐Cell Lymphoma, Nasal Type: A Prospective Cohort Study
Quanguang Ren, Yue Cui, He Huang, Xueying Li, Huangming Hong, Zhao Wang, Xiaojie Fang, Chengcheng Guo, Yuyi Yao, Zegeng Chen, Ying Huang, Zhiming Li, Qingqing Cai, Ying Tian, Hanyu Wang, Xiaoping Lin, Wei Fan, Lie Zheng, Suxia Lin, Ying Guo, Tongyu Lin
Head & Neck.2025; 47(9): 2392. CrossRef

4,013 View
117 Download
1 Crossref

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea: Ji Yun Lee, Ji Hyun Kwon, Joon Young Hur, Jun Ho Yi, Ji Hyun Lee, Hyungwoo Cho, Young Rok Do, Jae-Cheol Jo, Hye Jin Kang, Yougil Koh, Won Sik Lee, Sung Nam Lim, Sang Eun Yoon, Seok Jin Kim, Jeong-Ok Lee; Cancer Res Treat. 2024;56(2):681-687. Published online November 10, 2023; DOI: https://doi.org/10.4143/crt.2023.1042

Abstract PDF PubReader ePub

Purpose
Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers.
Materials and Methods
Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022.
Results
The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs.
Conclusion
In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

Citations

Citations to this article as recorded by

An evaluation of sugemalimab for the treatment of relapsed or refractory extranodal natural killer T-cell lymphoma
Yingfang Feng, Xia Liu, Jingwei Yu, Zheng Song, Lanfang Li, Lihua Qiu, Shiyong Zhou, Zhengzi Qian, Xianhuo Wang, Huilai Zhang
Expert Opinion on Biological Therapy.2025; 25(1): 9. CrossRef
Early growth response 1 as a key regulator of PD-L1 expression and immune evasion in extranodal NK/T-cell lymphoma
Ji Yun Lee, Kui-Jin Kim, Woochan Park, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Tae Min Kim, Jin Ho Paik
Blood Cancer Journal.2025;[Epub] CrossRef
Efficacy of combined CD38 and PD-1 inhibition with isatuximab and cemiplimab for relapsed/refractory NK/T-cell lymphoma
Seok Jin Kim, Jing Quan Lim, Sang Eun Yoon, Deok-Hwan Yang, Ji Hyun Lee, Sung Yong Oh, Yoon Seok Choi, Seong Hyun Jeong, Min Kyoung Kim, Sung Nam Lim, Junhun Cho, Bon Park, Kyung Ju Ryu, Seunghyun Choi, Yoon Park, Kerry May Huifen Lim, Nur Ayuni Binte Muh
Blood.2025; 146(2): 155. CrossRef
Pembrolizumab

Reactions Weekly.2024; 2025(1): 390. CrossRef

5,448 View
237 Download
3 Web of Science
4 Crossref

Incidence and Features of Lymphoid Proliferation and Lymphomas after Solid Organ or Hematopoietic Stem Cell Transplantation in a National Database Cohort: Seung Min Hahn, Myeongjee Lee, JongHoon Hyun, Sungmin Lim, Ji-Man Kang, Jong Gyun Ahn, Dong Jin Joo, Inkyung Jung, Kyong Ihn; Cancer Res Treat. 2024;56(1):305-313. Published online July 18, 2023; DOI: https://doi.org/10.4143/crt.2023.647

Abstract PDF Supplementary Material PubReader ePub

Purpose
Post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic stem transplantation (HCT) or solid organ transplantation (SOT) result in poorer outcomes, including death. There are limited large cohort data on the incidence and natural course of PTLD in Asians.
Materials and Methods
We investigated PTLD using Korean national health insurance claims data of 47,518 patients who underwent HCT or SOT in 2008-2020. Patient demographics, time and type of PTLD diagnosis, type of PTLD treatment, and death data were collected. We used Fine and Gray subdistribution hazard models to calculate the cumulative incidence and risk factors for PTLD.
Results
During median follow-up of 5.32 years, PTLD occurred in 294 of 36,945 SOT patients (0.79%) and 235 of 10,573 HCT patients (2.22%). Cumulative incidence of PTLD were 0.49% at 1 year, 1.02% at 5 years, and 1.50% at 10 years post-transplantation. Age < 20 years (subdistribution hazard ratio [SHR] of 1.67 in age 10-19, SHR 1.51 in age 0-9), HCT (SHR 3.02), heart transplantation (SHR 2.27), and liver transplantation (SHR 1.47) were significant risk factors for PTLD. The presence of PTLD was associated with an increased risk of death (hazard ratio of 2.84). Overall, 5-year survival of PTLD patients was 68.9% (95% confidence interval, 64.9 to 73.2).
Conclusion
We observed a steady increase in PTLD over 10 years after HCT or SOT in this large cohort study. Pediatric age group, HCT, liver transplantation, and heart transplantation were suggested to be risk factors for PTLD, and PTLD was associated with a higher risk of death.

Citations

Citations to this article as recorded by

The Impact of Posttransplant Lymphoproliferative Disease in High-risk Kidney Transplant Recipients: Benefits of Prevention
Bryce A. Kiberd, Christopher J.A. Daley
Transplantation Direct.2025; 11(5): e1792. CrossRef
Does the Organ Matter in PTLD Development in Solid Organ Transplant Recipients? A Multicenter Observational Study of Risk and Prognostic Factors
Rafał Staros, Bartosz Foroncewicz, Dorota Kamińska, Dominika Dęborska-Materkowska, Sławomir Lizakowski, Izabela Zakrocka, Joanna Raszeja-Wyszomirska, Anita Stanjek-Cichoracka, Anna Pawłowska, Emilia Knioła, Paweł Poznański, Jolanta Gozdowska, Alicja Dębsk
Cancers.2025; 17(11): 1770. CrossRef
Malignancies After Renal Transplantation: Frequency, Etiology, and Prognosis—A Single Center Experience
Fatih Atalah, Aydın Acarbay, Akgün Karakök, Mehmet Beşiroğlu, Fatih Kuş, Huzeyfe Arıcı, Ahmet Burak Dirim, Vafa Suleymanova, Aydın Türkmen, Halil Yazıcı
Journal of Clinical Medicine.2025; 14(16): 5858. CrossRef

4,670 View
193 Download
3 Web of Science
3 Crossref

Circulating Tumor DNA Reflects Histologic and Clinical Characteristics of Various Lymphoma Subtypes: Jin Ju Kim, Hye Min Kim, Hongkyung Kim, Soo-Jeong Kim, Seung-Tae Lee, Jong Rak Choi, Saeam Shin, Doh Yu Hwang; Cancer Res Treat. 2024;56(1):314-323. Published online July 17, 2023; DOI: https://doi.org/10.4143/crt.2023.667

Abstract PDF Supplementary Material PubReader ePub

Purpose
We designed and evaluated the clinical performance of a plasma circulating tumor DNA (ctDNA) panel of 112 genes in various subtypes of lymphoma.
Materials and Methods
Targeted deep sequencing with an error-corrected algorithm was performed in ctDNA from plasma samples that were collected before treatment in 42 lymphoma patients. Blood buffy coat was utilized as a germline control. We evaluated the targeted gene panel using mutation detection concordance on the plasma samples with matched tissue samples analyzed the mutation profiles of the ctDNA.
Results
Next-generation sequencing analysis using matched tissue samples was available for 18 of the 42 patients. At least one mutation was detected in the majority of matched tissue biopsy samples (88.9%) and plasma samples (83.3%). A considerable number of mutations (40.4%) that were detected in the tissue samples were also found in the matched plasma samples. Majority of patients (21/42) were diffuse large B cell lymphoma patients. The overall detection rate of ctDNA in patients was 85.7% (36/42). The frequently mutated genes included PIM1, TET2, BCL2, KMT2D, KLHL6, HIST1H1E, and IRF8. A cutoff concentration (4,506 pg/mL) of ctDNA provided 88.9% sensitivity and 82.1% specificity to predict ctDNA mutation detection. The ctDNA concentration correlated with elevated lactate dehydrogenase level and the disease stage.
Conclusion
Our design panel can detect many actionable gene mutations, including those at low frequency. Therefore, liquid biopsy can be applied clinically in the evaluation of lymphoma patients, especially in aggressive lymphoma patients.

Citations

Citations to this article as recorded by

Circulating tumor DNA as a powerful tool in diagnostics and treatment outcome prediction – focus on large B–cell lymphomas and follicular lymphomas
Iva Hamova, Maria Maco, Anton Tkachenko, Kristyna Kupcova, Adriana Velasova, Marek Trneny, Heidi Mocikova, Ondrej Havranek
Expert Review of Molecular Diagnostics.2025; 25(6): 275. CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef

5,746 View
273 Download
2 Web of Science
2 Crossref

Lung and Thoracic cancer

First-Line Alectinib vs. Brigatinib in Advanced Non–Small Cell Lung Cancer with ALK Rearrangement: Real-World Data: Youngkyung Jeon, Sehhoon Park, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn; Cancer Res Treat. 2024;56(1):61-69. Published online July 14, 2023; DOI: https://doi.org/10.4143/crt.2023.461

Abstract PDF PubReader ePub

Purpose
Alectinib and brigatinib are second-generation anaplastic lymphoma receptor tyrosine kinases (ALKs) that are widely used as first-line therapy for treating ALK-positive advanced non–small cell lung cancer (NSCLC). Given the lack of a head-to-head comparison of these drugs as first-line therapies, this retrospective observational study aimed to compare the real-world efficacy and safety of alectinib and brigatinib.
Materials and Methods
Patients who received alectinib or brigatinib as the first-line treatment for ALK-positive advanced NSCLC were evaluated for clinical outcomes of objective response rate (ORR), intracranial ORR, time to next treatment (TTNT), progression-free survival (PFS), overall survival (OS), and safety profiles.
Results
Of 208 patients who received either alectinib or brigatinib as a first-line treatment, 176 received alectinib and 32 received brigatinib. At the data cutoff point, the median follow-up duration was 16.5 months (95% confidence interval [CI], 14.7 to 18.3) in the brigatinib group and 27.5 months (95% CI, 24.6 to 30.4) in the alectinib group. The ORR was 92.5% with alectinib and 93.8% for brigatinib. The intracranial ORR rates were 92.7% (38/41) and 100% (10/10), respectively. The rate of PFS at 12 months was comparable between the alectinib group and the brigatinib groups (84.4% vs. 84.1%, p=0.64), and the median TTNT, PFS, and OS were not reached in either group. Treatment-related adverse events were usually mild, and treatment discontinuation due to adverse events was rare (alectinib 4.5% vs. brigatinib 6.25%).
Conclusion
Alectinib and brigatinib had similar clinical benefits when used as the first-line treatment of NSCLC patients with ALK rearrangement in the real world.

Citations

Citations to this article as recorded by

Efficacy and safety of brigatinib in patients with ALK TKI-naive advanced ALK+ NSCLC: Integrated analysis of the ALTA-1L and J-ALTA trials
D. Ross Camidge, Shunichi Sugawara, Masashi Kondo, Hye Ryun Kim, Myung-Ju Ahn, James C.H. Yang, Ji-Youn Han, Maximilian J. Hochmair, Ki Hyeong Lee, Angelo Delmonte, Kentarou Kudou, Takayuki Asato, Bradley Hupf, Florin Vranceanu, Robert J. Fram, Yuichiro O
Lung Cancer.2025; 201: 108424. CrossRef
Effectiveness of First-Line Treatment with Anaplastic Lymphoma Kinase and ROS1 Protoncogene Inhibitors in Non-Small Cell Lung Cancer Patients—Real-World Evidence of Two Polish Cancer Centers
Michał Gil, Kinga Winiarczyk, Paweł Krawczyk, Kamila Wojas-Krawczyk, Aleksandra Łomża-Łaba, Adrian Obara, Łukasz Gajek, Katarzyna Reszka, Andrzej Tysarowski, Jarosław Buczkowski, Izabela Chmielewska, Tomasz Jankowski, Magdalena Szuba-Gil, Maciej Strzemski
Cancers.2025; 17(7): 1253. CrossRef
Oncogenic Fusions in NSCLC: From Mechanisms to Clinical Applications
Nyein Wint Yee Theik, Suset Almuinas De Armas, Daniel Rosas, Amy Kiamos, Nyein Nyein Thaw Dar, Ahmed Shoreibah, Atif Hussein, Luis E. Raez
International Journal of Molecular Sciences.2025; 26(8): 3802. CrossRef
Real World Data on the Efficacy of Brigatinib in ALK-Positive Non-Small Cell Lung Cancer: A Single-Center Experience
Vesna Ćeriman Krstić, Natalija Samardžić, Mihailo Stjepanović, Spasoje Popević, Tatjana Adžić-Vukičević, Sofija Glumac, Ruža Stević, Dragana Marić, Marta Velinović, Milena Jovanović, Branislav Ilić, Milija Gajić, Nikola Čolić, Katarina Lukić, Brankica Mil
Cancers.2025; 17(18): 3084. CrossRef
Real‐World Outcomes of Brigatinib Compared to Alectinib as a Second‐Line Therapy After Crizotinib in Advanced Anaplastic Lymphoma Kinase Positive Non‐Small Cell Lung Cancer Patients
Min Jee Kim, Hyun Seok Kwak, Eun Nim Koh, Cheol‐Kyu Park, Young‐Chul Kim, In‐Jae Oh, Seung Joon Kim, Jun Hyeok Lim, Jeong‐Seon Ryu, Chang Min Choi
Thoracic Cancer.2025;[Epub] CrossRef
Bridging the Gap between Trial Adverse Events and Real-World Data
Sang Hyuk Kim, Hyun Lee, Dong Won Park
Cancer Research and Treatment.2024; 56(3): 972. CrossRef
Real‐world evidence of brigatinib as second‐line treatment after crizotinib for ALK+ non‐small cell lung cancer using South Korean claims data (K‐AREAL)
Jeong Eun Lee, Jin Hyun Nam, Sun Hong Kwon, Bo Kyung Kim, Seung Min Ha
Cancer Medicine.2024;[Epub] CrossRef
Cost‐Effectiveness Analysis of Adjuvant Alectinib versus Platinum‐Based Chemotherapy in Resected ALK‐Positive Non‐Small‐Cell Lung Cancer in the Chinese Health Care System
Qiran Wei, Yifang Liang, Jiahui Mao, Xin Guan
Cancer Medicine.2024;[Epub] CrossRef

7,682 View
645 Download
9 Web of Science
8 Crossref

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

Abstract PDF PubReader ePub

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

Citations to this article as recorded by

CAR-T cell therapy in the treatment of relapsed or refractory primary central nervous system lymphoma: recent advances and challenges
Shuzhen Xiong, Shuni Zhang, Ningning Yue, Jiajia Cao, Chongyang Wu
Leukemia & Lymphoma.2025; 66(6): 1045. CrossRef
New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma
Chuanwei Yang, Xiaohui Ren, Yong Cui, Haihui Jiang, Ming Li, Kefu Yu, Shaoping Shen, Mingxiao Li, Xiaokang Zhang, Xuzhe Zhao, Qinghui Zhu, Xingyao Bu, Song Lin
Frontiers in Immunology.2025;[Epub] CrossRef
Successful CD19 chimeric antigen receptor T-cell therapy following autologous stem cell transplantation in a secondary central nervous system lymphoma patient with COVID-19 infection: a case report and literature review
Xiaoning Wang, Juan Ren, Yuqi Wang, Minna Luo, Jing Li, Pengcheng He
Frontiers in Oncology.2025;[Epub] CrossRef
The Landscape of Primary Central Nervous System Lymphoma (PCNSL): Clinicopathologic and Genomic Characteristics and Therapeutic Perspectives
Huijuan Jiang, Lin Nong
Cancers.2025; 17(17): 2909. CrossRef
Targeting PD-L1 for PCNS-DLBCL: from molecular effects to clinical translation
Jiajia Cao, Shuzhen Xiong, Shuni Zhang, Ningning Yue, Chongyang Wu
Frontiers in Immunology.2025;[Epub] CrossRef
Are we ready for personalizedCAR‐Ttherapy?
Anna Strzelec, Grzegorz Helbig
European Journal of Haematology.2024; 112(2): 174. CrossRef
Tislelizumab augment the efficacy of CD19/22 dual‐targeted chimeric antigen receptor T cell in advanced stage relapsed or refractory B‐cell non‐Hodgkin lymphoma
Ying Zhang, Hongzhi Geng, Liangyu Zeng, Jiaqi Li, Qin Yang, Sixun Jia, Xiangping Zong, Wenzhi Cai, Shuangzhu Liu, Yutong Lu, Lei Yu, Caixia Li, Depei Wu
Hematological Oncology.2024;[Epub] CrossRef
Therapeutic targeting of DNA methylation alterations in cancer
Abigail V. Lee, Kevin A. Nestler, Katherine B. Chiappinelli
Pharmacology & Therapeutics.2024; 258: 108640. CrossRef
Cytarabine/methotrexate/rituximab

Reactions Weekly.2024; 2003(1): 302. CrossRef
A systematic review of primary central nervous system lymphoma
Lei Zhang, Qingyuan Zhang
Holistic Integrative Oncology.2024;[Epub] CrossRef
The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review
Bibhu Prasad Satapathy, Pooja Sheoran, Rohit Yadav, Dewan Chettri, Dhruba Sonowal, Chinmayee Priyadarsini Dash, Prachi Dhaka, Vivek Uttam, Ritu Yadav, Manju Jain, Aklank Jain
Frontiers in Immunology.2024;[Epub] CrossRef
Siglecs-mediated immune regulation in neurological disorders
Huifang Tu, Limei Yuan, Bo Ni, Yufeng Lin, Kaiyuan Wang
Pharmacological Research.2024; 210: 107531. CrossRef

6,194 View
258 Download
11 Web of Science
12 Crossref

Hematologic malignancy

Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study: Yu Ri Kim, Jin Seok Kim, Won Seog Kim, Hyeon Seok Eom, Deok-Hwan Yang, Sung Hwa Bae, Hyo Jung Kim, Jae Hoon Lee, Suk-Joong Oh, Sung-Soo Yoon, Jae-Yong Kwak, Chul Won Choi, Min Kyoung Kim, Sung Young Oh, Hye Jin Kang, Seung Hyun Nam, Hyeok Shim, Joon Seong Park, Yeung-Chul Mun, Cheolwon Suh, the Korean Society of Hematology Lymphoma Working Party; Cancer Res Treat. 2023;55(4):1355-1362. Published online March 30, 2023; DOI: https://doi.org/10.4143/crt.2023.271

Abstract PDF Supplementary Material PubReader ePub

Purpose
This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL).
Materials and Methods
Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy.
Results
Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016).
Conclusion
Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Citations

Citations to this article as recorded by

Design, Conduct, and Analysis of Externally Controlled Trials
Jiali Liu, Minghong Yao, Mingqi Wang, Wan Jie, Yanmei Liu, Xiaochao Luo, Jiayidaer Huan, Kelin Deng, Ke Deng, Kang Zou, Ying Zhang, Ling Li, Xin Sun
JAMA Network Open.2025; 8(9): e2530277. CrossRef

6,376 View
273 Download
1 Web of Science
1 Crossref

Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis: Jinchul Kim, Jinhyun Cho, Sang Eun Yoon, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2023;55(3):1031-1047. Published online March 13, 2023; DOI: https://doi.org/10.4143/crt.2022.1658

Abstract PDF Supplementary Material PubReader ePub

Purpose
We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis.
Materials and Methods
R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment.
Results
Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment.
Conclusion
Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.

Citations

Citations to this article as recorded by

Real-World Effectiveness of Chemoimmunotherapy and Novel Therapies for Patients With Relapsed/Refractory Aggressive Large B-Cell Lymphoma
Loretta J. Nastoupil, Clark R. Andersen, Amy Ayers, Yucai Wang, Thomas M. Habermann, Dai Chihara, Brad S. Kahl, Brian K. Link, Jean L. Koff, Jonathon B. Cohen, Peter Martin, Izidore S. Lossos, Michele Stanchina, Sara Haddadi, Carla Casulo, Sabarish Ayyapp
Clinical Lymphoma Myeloma and Leukemia.2025; 25(4): e183. CrossRef
Efficacy and safety of polatuzumab-vedotin plus bendamustine and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma: A systematic review and meta-analysis
Hanzala Ahmed Farooqi, Muhammad Saffi Ullah, Ahmed Raza, Zain Sadiq, Wardah Ali Shaikh, Rahmah Muhammad, Muhammad Shoaib Hussain
Critical Reviews in Oncology/Hematology.2025; 207: 104611. CrossRef
Efficacy and Safety of Chimeric Antigen Receptor (CAR)-T Cell Therapy in Patients with Non-Hodgkin Lymphoma
Abdur Jamil, Zaheer Qureshi, Rimsha Siddique, Faryal Altaf, Hamzah Akram, Rohma Jamil, Shehroz Aslam, Insija I. Selene
American Journal of Clinical Oncology.2025; 48(5): 262. CrossRef
Improving access to chimeric antigen receptor T-cells for refractory or relapsing diffuse large B cell lymphoma therapy in Asia
Ya Hwee Tan, Dok Hyun Yoon, Andrew J. Davies, Christian Buske, Yang Liang Boo, Nagavalli Somasundaram, Francesca Lim, Shin Yeu Ong, Anand Jeyasekharan, Koji Izutsu, Won Seog Kim, Jason Yongsheng Chan
Discover Oncology.2025;[Epub] CrossRef
Luteolin inhibits diffuse large B-cell lymphoma cell growth through the JAK2/STAT3 signaling pathway
Xin-Zhuo Zhan, Yi-Wen Bo, Yu Zhang, Hai-Dong Zhang, Zhi-Hao Shang, Hui Yu, Xiao-Li Chen, Xiang-Tu Kong, Wan-Zhou Zhao, Timo Teimonen, Tao Liu, Meng-Yi Lu, Ye Yang, Shan-Liang Sun, Hai-Wen Ni
Frontiers in Pharmacology.2025;[Epub] CrossRef
Heavily Pretreated Refractory Diffuse Large B-Cell Lymphoma Successfully Treated with Epcoritamab: Case Report
Jeremy Rosiecki, Natalie Wallace, Katelyn Kammers, Ann-Chee Cheng, Talia Wyckoff, Steven Liu
Case Reports in Oncology.2025; 18(1): 744. CrossRef
Efficacy and safety of chimeric antigen receptor T-cell in the treatment of hematologic malignancy: an umbrella review of systematic review and meta-analysis
Zhengyu Yu, Caixia Jing, Li Xie, Lang Min, Lingfeng Li, Zhongwang Wang, Ting Niu
Frontiers in Immunology.2025;[Epub] CrossRef
Polatuzumab vedotin combined with bendamustine and rituximab for relapsed/refractory diffuse large B-cell lymphoma: A systematic review protocol
Mohammadreza Eslami, Mahdi Mehrabi, Mehrdad Payandeh, Fakhredin Saba, Chen Li
PLOS ONE.2024; 19(8): e0308247. CrossRef
Clinical scoring systems, molecular subtypes and baseline [18F]FDG PET/CT image analysis for prognosis of diffuse large B-cell lymphoma
Zhuxu Sun, Tianshuo Yang, Chongyang Ding, Yuye Shi, Luyi Cheng, Qingshen Jia, Weijing Tao
Cancer Imaging.2024;[Epub] CrossRef
Targeting CD22 for B-cell hematologic malignancies
Jia Xu, Wenjing Luo, Chenggong Li, Heng Mei
Experimental Hematology & Oncology.2023;[Epub] CrossRef

10,958 View
723 Download
10 Web of Science
10 Crossref

Search