RARE DISEASE
Primary mediastinal large B-cell lymphoma
Primary mediastinal large B-cell lymphoma
Primary mediastinal large B-cell lymphoma
Synonyms: Large cell lymphoma of the mediastinum, Med-DLBCL, Mediastinal diffuse large-cell lymphoma with sclerosis, Primary mediastinal clear cell lymphoma of B-cell type
Synonyms: Large cell lymphoma of the mediastinum, Med-DLBCL, Mediastinal diffuse large-cell lymphoma with sclerosis, Primary mediastinal clear cell lymphoma of B-cell type
Synonyms: Large cell lymphoma of the mediastinum, Med-DLBCL, Mediastinal diffuse large-cell lymphoma with sclerosis, Primary mediastinal clear cell lymphoma of B-cell type
Drug discovery
8
drugs
With orphan designations
Overview
Primary mediastinal large B-cell lymphoma (PMBCL) is a rare, aggressive non-Hodgkin lymphoma arising in the mediastinum, accounting for 2%-4% of NHL cases [1][7][15]. It primarily affects young adults (median age 35) with a female predominance (2:1 ratio) [2][3][12][20]. Clinical presentation often includes superior vena cava syndrome due to bulky tumors (>10 cm) compressing thoracic structures [7][9][15][20]. Diagnosis relies on histopathology showing CD20+/CD30± B-cells with fibrotic stroma [1][7][15]. First-line therapy achieves >80% 5-year survival using R-CHOP or R-EPOCH regimens, with PET-guided radiation consolidation [3][8][13][17].
Burden
23% develop chemotherapy-resistant relapse [12][17]; radiation-associated cardiovascular toxicity in 40% of long-term survivors [1][13]; 14% 5-year mortality despite improved therapies [12][15]
Emerging targeted therapies and response-adapted approaches aim to reduce late complications while maintaining efficacy [3][8][15][17].
Therapies
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
466 drug discovery papers about Primary mediastinal large B-cell lymphoma, with 1 first-in-class and 9 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
466 drug discovery papers about Primary mediastinal large B-cell lymphoma, with 1 first-in-class and 9 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-30 | Allogeneic hematopoietic stem cell transplantation achieves complete response in refractory primary mediastinal large B-cell lymphoma after the failure of chemotherapy, CAR-T therapy, and PD-1 blockade.
Primary mediastinal large B-cell lymphoma (PMBCL) typically responds to chemotherapy, and immunotherapies such as chimeric antigen receptor T-cell (CAR-T) therapy and the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab have shown promise in relapsed or refractory cases. However, the sequential use of multiple immunotherapies for PMBCL remains poorly characterized. Here, we report a case of a 19-year-old female with PMBCL involving the mediastinum and multiple extranodal sites. After a partial response to chemotherapy, she developed a central nervous system relapse that responded to high-dose methotrexate, and the number of regrowing mediastinal lesions was reduced by radiotherapy. Subsequently, new hepatic lesions that were refractory to both CAR-T therapy and pembrolizumab emerged. Following localized liver radiotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed, resulting in complete response. Early post-transplant, she developed a hepatitis variant of acute graft-versus-host disease, which may have reflected a graft-versus-lymphoma (GVL) effect. Despite maintaining response, the patient died one year later form a disseminated infection with multitriazole-resistant Aspergillus fumigatus. This case highlights both the potential curative role and the substantial risks of allo-HSCT in PMBCL refractory to multiple immunotherapies. The pre-transplant use of pembrolizumab and localized radiotherapy may influence transplant outcomes and warrants further investigation.
2026-07-06 | Successful Postpartum CAR T-cell Salvage Therapy for Primary Mediastinal Large B-cell Lymphoma with Residual Disease after R-CHOP During Pregnancy.
Primary mediastinal large B-cell lymphoma (PMBCL) during pregnancy is rare and presents therapeutic challenges due to fetal safety concerns. We report the case of a 29-year-old woman diagnosed with PMBCL at 19 weeks of gestation who wished to continue her pregnancy despite her diagnosis. She received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy with multidisciplinary management and delivered a healthy infant at term. Although the tumor partially responded, residual disease persisted after eight cycles of treatment. She subsequently underwent chimeric antigen receptor T-cell therapy and achieved a complete response. This case highlights the importance of individualized treatment decisions and multidisciplinary collaboration in managing PMBCL during pregnancy.
2026-07-02 | PD-L2 is associated with lineage-related transcriptional programs distinct from PD-L1 in primary mediastinal large B-cell lymphoma.
Primary mediastinal large B-cell lymphoma (PMBCL) is characterized by recurrent 9p24.1 alterations driving constitutive overexpression of PD-1 ligands and high sensitivity to PD-1 blockade. While PD-L1 is widely used as a biomarker, the tumor-intrinsic functions of PD-1 ligands, and particularly PD-L2, remain poorly defined. Here, we investigated the distinct roles of PD-L1 and PD-L2 in PMBCL using CRISPR-Cas9-engineered isogenic models, immune co-culture assays, an immune-interactive in ovo chorioallantoic membrane (CAM) xenograft system, and integrative transcriptomic analyses of patient datasets. PD-L1 was most strongly associated with restraint of Th1-associated immune signaling and influenced responsiveness to PD-1 blockade, whereas PD-L2 was associated with preservation of lineage-associated transcriptional programs and distinct treatment-response patterns. Combined disruption of both ligands enhanced Th1 immune activation while altering B-cell transcriptional states. Consistent with these findings, transcriptomic analyses in PMBCL cohorts linked PDCD1LG2 expression to B-cell identity and signaling modules, whereas CD274 expression aligned with interferon-responsive immune programs. Together, these results support a model in which PD-L1 and PD-L2 associate with distinct immune and lineage-associated states in PMBCL and provide a framework for exploring biologically informed stratification strategies in this disease.
2026-06-26 | Dose-Adjusted EPOCH-R in Aggressive B-Cell Lymphomas: Efficacy, Molecular Prognostic Factors, and Real-World Outcomes from a Multicenter Turkish Cohort-A Turkish Oncology Group (TOG) Study.
Background and Objectives: Comprehensive real-world data on dose-adjusted EPOCH-R (DA-EPOCH-R) incorporating molecular prognostic stratification remain limited. We evaluated the long-term efficacy, safety, and prognostic determinants of DA-EPOCH-R in a multicenter Turkish cohort. Materials and Methods: This retrospective study included 140 patients with aggressive B-cell lymphoma (diffuse large B-cell lymphoma [DLBCL], n = 81; primary mediastinal B-cell lymphoma [PMBL], n = 39; other, n = 20) treated with DA-EPOCH-R at five academic centers (2015-2020). Molecular profiling included immunohistochemistry (MYC, BCL-2, BCL-6) and fluorescence in situ hybridization (FISH). Survival was estimated by Kaplan-Meier analysis with Cox regression for prognostic factors. Results: At a median follow-up of 50.1 months, 5-year overall survival (OS) and event-free survival (EFS) rates were 71.3% and 66.3%, respectively (complete response rate: 68.6%). Molecular subtypes included double-expressor (DEL; n = 39), triple-expressor (TEL; n = 21), double-hit (DHL; n = 17), and triple-hit lymphoma (THL; n = 11). Five-year OS by IPI risk group ranged from 88.6% (low) to 49.4% (high) (p = 0.005). DEL status did not confer inferior OS (p = 0.738), whereas DHL and THL had markedly poor outcomes (p < 0.001). In multivariate analysis, IPI ≥ 3 (HR 2.54; p = 0.007) and MYC FISH rearrangement (HR 3.62; p < 0.001) independently predicted inferior OS. Grade 3-4 neutropenia occurred in 57.1%, with no grade 3-4 cardiotoxicity. Conclusions: DA-EPOCH-R provides favorable long-term outcomes in aggressive B-cell lymphomas. DEL status did not confer a survival disadvantage, an association that is hypothesis-generating and requires confirmation, as the present design cannot establish a causal mechanism. FISH-defined DHL/THL remain associated with dismal outcomes, warranting novel therapeutic strategies.
2026-06-10 | Primary mediastinal large B cell lymphoma in pregnancy: a case report and review of the literature.
Primary mediastinal B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that typically presents as a large mass originating in the mediastinum and infiltrating the surrounding organs, resulting in pleural and pericardial effusions. The occurrence of PMBCL during pregnancy presents a significant challenge to clinical management, necessitating a comprehensive consideration of the unique risks posed to both the pregnant woman and the foetus when selecting the optimal treatment. This report presents cases of PMBCL diagnosed during late pregnancy and reviews the pertinent literature, emphasising the necessity of prompt diagnosis and the implementation of tailored management strategies for different stages of pregnancy to enhance pregnancy outcomes. A 29-year-old woman with four documented pregnancies, yet no documented deliveries. At 15 weeks' gestation, the patient presented at the local hospital with a cough, which was diagnosed as an upper respiratory tract infection. She was treated with oral antibiotics; however, there was no significant improvement in her condition. During the 28th week of gestation, the patient's respiratory distress and dysphagia worsened, and she was unable to assume a recumbent position. The patient was admitted to our hospital with a computed tomography scan indicating the presence of a sizable mediastinal mass. Given the potential risks, benefits, and recent status, a decision was made to perform an emergency caesarean section. The procedure resulted in the successful delivery of the foetus, with Apgar scores of 6, 7, and 7 at 1, 5, and 10 minutes, respectively. A comprehensive examination of the neonate revealed no additional abnormalities and demonstrated normal developmental progress after a period of over four months. Following delivery, the diagnosis of PMBCL was confirmed by puncture biopsy of the mediastinal mass and PET-CT. The pregnant woman then received five doses of DA-EPOCH-R chemotherapy, resulting in a significant reduction of the mediastinal mass and remission of her symptoms. This case study illustrates the significant challenges associated with diagnosing and treating Primary mediastinal B-cell lymphoma during pregnancy. In this rare and complex case, the timing of termination of pregnancy and the choice of treatment regimen are of critical importance in order to improve maternal and infant outcomes.
2026-07-30 | Allogeneic hematopoietic stem cell transplantation achieves complete response in refractory primary mediastinal large B-cell lymphoma after the failure of chemotherapy, CAR-T therapy, and PD-1 blockade.
Primary mediastinal large B-cell lymphoma (PMBCL) typically responds to chemotherapy, and immunotherapies such as chimeric antigen receptor T-cell (CAR-T) therapy and the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab have shown promise in relapsed or refractory cases. However, the sequential use of multiple immunotherapies for PMBCL remains poorly characterized. Here, we report a case of a 19-year-old female with PMBCL involving the mediastinum and multiple extranodal sites. After a partial response to chemotherapy, she developed a central nervous system relapse that responded to high-dose methotrexate, and the number of regrowing mediastinal lesions was reduced by radiotherapy. Subsequently, new hepatic lesions that were refractory to both CAR-T therapy and pembrolizumab emerged. Following localized liver radiotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed, resulting in complete response. Early post-transplant, she developed a hepatitis variant of acute graft-versus-host disease, which may have reflected a graft-versus-lymphoma (GVL) effect. Despite maintaining response, the patient died one year later form a disseminated infection with multitriazole-resistant Aspergillus fumigatus. This case highlights both the potential curative role and the substantial risks of allo-HSCT in PMBCL refractory to multiple immunotherapies. The pre-transplant use of pembrolizumab and localized radiotherapy may influence transplant outcomes and warrants further investigation.
2026-07-06 | Successful Postpartum CAR T-cell Salvage Therapy for Primary Mediastinal Large B-cell Lymphoma with Residual Disease after R-CHOP During Pregnancy.
Primary mediastinal large B-cell lymphoma (PMBCL) during pregnancy is rare and presents therapeutic challenges due to fetal safety concerns. We report the case of a 29-year-old woman diagnosed with PMBCL at 19 weeks of gestation who wished to continue her pregnancy despite her diagnosis. She received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy with multidisciplinary management and delivered a healthy infant at term. Although the tumor partially responded, residual disease persisted after eight cycles of treatment. She subsequently underwent chimeric antigen receptor T-cell therapy and achieved a complete response. This case highlights the importance of individualized treatment decisions and multidisciplinary collaboration in managing PMBCL during pregnancy.
2026-07-02 | PD-L2 is associated with lineage-related transcriptional programs distinct from PD-L1 in primary mediastinal large B-cell lymphoma.
Primary mediastinal large B-cell lymphoma (PMBCL) is characterized by recurrent 9p24.1 alterations driving constitutive overexpression of PD-1 ligands and high sensitivity to PD-1 blockade. While PD-L1 is widely used as a biomarker, the tumor-intrinsic functions of PD-1 ligands, and particularly PD-L2, remain poorly defined. Here, we investigated the distinct roles of PD-L1 and PD-L2 in PMBCL using CRISPR-Cas9-engineered isogenic models, immune co-culture assays, an immune-interactive in ovo chorioallantoic membrane (CAM) xenograft system, and integrative transcriptomic analyses of patient datasets. PD-L1 was most strongly associated with restraint of Th1-associated immune signaling and influenced responsiveness to PD-1 blockade, whereas PD-L2 was associated with preservation of lineage-associated transcriptional programs and distinct treatment-response patterns. Combined disruption of both ligands enhanced Th1 immune activation while altering B-cell transcriptional states. Consistent with these findings, transcriptomic analyses in PMBCL cohorts linked PDCD1LG2 expression to B-cell identity and signaling modules, whereas CD274 expression aligned with interferon-responsive immune programs. Together, these results support a model in which PD-L1 and PD-L2 associate with distinct immune and lineage-associated states in PMBCL and provide a framework for exploring biologically informed stratification strategies in this disease.
2026-06-26 | Dose-Adjusted EPOCH-R in Aggressive B-Cell Lymphomas: Efficacy, Molecular Prognostic Factors, and Real-World Outcomes from a Multicenter Turkish Cohort-A Turkish Oncology Group (TOG) Study.
Background and Objectives: Comprehensive real-world data on dose-adjusted EPOCH-R (DA-EPOCH-R) incorporating molecular prognostic stratification remain limited. We evaluated the long-term efficacy, safety, and prognostic determinants of DA-EPOCH-R in a multicenter Turkish cohort. Materials and Methods: This retrospective study included 140 patients with aggressive B-cell lymphoma (diffuse large B-cell lymphoma [DLBCL], n = 81; primary mediastinal B-cell lymphoma [PMBL], n = 39; other, n = 20) treated with DA-EPOCH-R at five academic centers (2015-2020). Molecular profiling included immunohistochemistry (MYC, BCL-2, BCL-6) and fluorescence in situ hybridization (FISH). Survival was estimated by Kaplan-Meier analysis with Cox regression for prognostic factors. Results: At a median follow-up of 50.1 months, 5-year overall survival (OS) and event-free survival (EFS) rates were 71.3% and 66.3%, respectively (complete response rate: 68.6%). Molecular subtypes included double-expressor (DEL; n = 39), triple-expressor (TEL; n = 21), double-hit (DHL; n = 17), and triple-hit lymphoma (THL; n = 11). Five-year OS by IPI risk group ranged from 88.6% (low) to 49.4% (high) (p = 0.005). DEL status did not confer inferior OS (p = 0.738), whereas DHL and THL had markedly poor outcomes (p < 0.001). In multivariate analysis, IPI ≥ 3 (HR 2.54; p = 0.007) and MYC FISH rearrangement (HR 3.62; p < 0.001) independently predicted inferior OS. Grade 3-4 neutropenia occurred in 57.1%, with no grade 3-4 cardiotoxicity. Conclusions: DA-EPOCH-R provides favorable long-term outcomes in aggressive B-cell lymphomas. DEL status did not confer a survival disadvantage, an association that is hypothesis-generating and requires confirmation, as the present design cannot establish a causal mechanism. FISH-defined DHL/THL remain associated with dismal outcomes, warranting novel therapeutic strategies.
2026-06-10 | Primary mediastinal large B cell lymphoma in pregnancy: a case report and review of the literature.
Primary mediastinal B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) that typically presents as a large mass originating in the mediastinum and infiltrating the surrounding organs, resulting in pleural and pericardial effusions. The occurrence of PMBCL during pregnancy presents a significant challenge to clinical management, necessitating a comprehensive consideration of the unique risks posed to both the pregnant woman and the foetus when selecting the optimal treatment. This report presents cases of PMBCL diagnosed during late pregnancy and reviews the pertinent literature, emphasising the necessity of prompt diagnosis and the implementation of tailored management strategies for different stages of pregnancy to enhance pregnancy outcomes. A 29-year-old woman with four documented pregnancies, yet no documented deliveries. At 15 weeks' gestation, the patient presented at the local hospital with a cough, which was diagnosed as an upper respiratory tract infection. She was treated with oral antibiotics; however, there was no significant improvement in her condition. During the 28th week of gestation, the patient's respiratory distress and dysphagia worsened, and she was unable to assume a recumbent position. The patient was admitted to our hospital with a computed tomography scan indicating the presence of a sizable mediastinal mass. Given the potential risks, benefits, and recent status, a decision was made to perform an emergency caesarean section. The procedure resulted in the successful delivery of the foetus, with Apgar scores of 6, 7, and 7 at 1, 5, and 10 minutes, respectively. A comprehensive examination of the neonate revealed no additional abnormalities and demonstrated normal developmental progress after a period of over four months. Following delivery, the diagnosis of PMBCL was confirmed by puncture biopsy of the mediastinal mass and PET-CT. The pregnant woman then received five doses of DA-EPOCH-R chemotherapy, resulting in a significant reduction of the mediastinal mass and remission of her symptoms. This case study illustrates the significant challenges associated with diagnosing and treating Primary mediastinal B-cell lymphoma during pregnancy. In this rare and complex case, the timing of termination of pregnancy and the choice of treatment regimen are of critical importance in order to improve maternal and infant outcomes.
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Drug Discovery Landscape
8 orphan drug designations for Primary mediastinal large B-cell lymphoma, including 4 approved therapies.
8 orphan drug designations for Primary mediastinal large B-cell lymphoma, including 4 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Surovatamig | antibodies | EMA | 2026-04-20 | — | AstraZeneca AB |
Methotrexate | — | EMA | 2025-08-22 | — | Helio Vision Germany GmbH |
nivolumab | antibodies | FDA | 2019-02-01 | — | Bristol-Myers Squibb Company |
Lisocabtagene maraleucel [Breyanzi] | cell therapies | EMA | 2018-11-20 | — | Bristol-Myers Squibb Pharma EEIG |
lisocabtagene maraleucel [Breyanzi] | cell therapies | FDA | 2018-07-12 | 2021-02-05 | Juno Therapeutics, Inc., a Bristol-Myers Squibb Company |
axicabtagene ciloleucel [Yescarta] | cell therapies | FDA | 2016-04-20 | 2017-10-18 | Kite Pharma, Inc. |
pembrolizumab [Keytruda] | antibodies | FDA | 2016-01-14 | 2018-06-13 | MSD International Business GmbH |
Autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3-zeta chimeric antigen receptor [Yescarta] | cell therapies | EMA | 2015-10-09 | 2018-08-27 | Kite Pharma EU B.V. |
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