RARE DISEASE
B-cell non-Hodgkin lymphoma
B-cell non-Hodgkin lymphoma
B-cell non-Hodgkin lymphoma
Synonyms: B-cell NHL
Synonyms: B-cell NHL
Synonyms: B-cell NHL
Drug discovery
7
drugs
With orphan designations
Overview
B-cell non-Hodgkin lymphoma (B-NHL) comprises over 70 subtypes of lymphoid malignancies arising from genetically mutated B lymphocytes. These cancers typically involve lymph nodes or extranodal sites, with behavior ranging from indolent (e.g., follicular lymphoma) to aggressive (e.g., diffuse large B-cell lymphoma). Treatment strategies depend on histology, stage, and molecular markers, incorporating immunotherapy (e.g., anti-CD20 monoclonal antibodies), chemotherapy, targeted agents, and CAR-T cell therapy [1][3][4][7][19].
Therapies
Frontline: R-CHOP (rituximab+chemotherapy) for aggressive subtypes; radiation/obinutuzumab for localized disease [4][7][19]
Relapsed/Refractory: CAR-T therapy (e.g., axicabtagene ciloleucel), bispecific antibodies (e.g., mosunetuzumab), BTK inhibitors [3][7][15][19]
Emerging: CD19/CD20-targeted therapies, combination regimens with lenalidomide [3][15][20]
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
2,815 drug discovery papers about B-cell non-Hodgkin lymphoma, with 7 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,815 drug discovery papers about B-cell non-Hodgkin lymphoma, with 7 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-15 | SOHO State of the Art Updates and Next Questions| Mediastinal Gray-zone Lymphoma: Novel Biologic Insights and Updates on How Best to Approach This Rare Entity.
Mediastinal gray zone lymphoma (MGZL) is a very rare aggressive B-cell non-Hodgkin lymphoma characterized by clinical, pathologic, and molecular features that overlap between nodular sclerosis Hodgkin lymphoma (NSHL) and primary mediastinal B-cell lymphoma (PMBL). While these are clinically related lymphomas, recent molecular profiling studies demonstrated similarities between these 3 entities, including alterations in the nuclear factor-κB pathway, JAK2/STAT signaling, copy number alterations in 9p24.1, and immune evasion. In the most recent WHO-5 and ICC classifications, the definition of GZL was restricted to mediastinal GZL (MGZL), which remains as a separate entity between NSHL and PMBL; however, non-mediastinal GZL was classified under diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS). Given the rarity of the disease, evolving definition, and diagnostic challenges, few prospective studies have been undertaken to evaluate treatment outcomes. Response rates and survival with frontline chemotherapy are inferior compared to PMBL, and retrospective studies suggest superiority of dose-intensive regimens compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in MGZL. Despite recent therapeutic advancements in PMBL and classical Hodgkin lymphoma (cHL), most clinical trials have excluded patients with MGZL, leading to uncertainty regarding the best therapeutic strategy in both the frontline and relapsed/refractory settings.
2026-08-13 | The Role of Direct-Acting Antivirals (DAAs) in Hepatitis C Virus-Associated Lymphoproliferative Disorders.
Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, affecting approximately 50 million people worldwide. An estimated 15-30% of individuals with chronic HCV infection progress to cirrhosis, which may subsequently develop into hepatocellular carcinoma. Beyond liver disease, HCV is associated with a broad spectrum of extrahepatic manifestations, particularly mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). Persistent viral infection induces chronic antigenic stimulation of B lymphocytes, a key pathogenic mechanism underlying the progression from MC to overt B-NHL. These observations have important therapeutic implications and support the use of antiviral therapy as a cornerstone of treatment. The efficacy of direct-acting antivirals (DAAs) has been well established in patients with HCV-related MC and cryoglobulinemic vasculitis. Several studies have shown that DAAs achieve sustained virologic response rates exceeding 90%, often approaching 100% in contemporary cohorts. Viral eradication is frequently associated with clinical and immunological improvement, as well as regression of cryoglobulinemia. Encouraging outcomes have also been reported in patients with HCV-associated indolent B-NHL, particularly marginal zone lymphoma, although confirmation in larger studies with longer follow-up is needed. In patients with HCV-positive aggressive lymphomas, DAAs have been safely administered in combination with immunochemotherapy, yielding promising results. This review summarizes the current evidence on HCV-associated MC and B-NHL and discusses the impact of DAA therapy on the clinical course and management of these disorders.
2026-07-31 | Mosunetuzumab: A bispecific CD20 × CD3 antibody for follicular lymphoma with promising evidence in other B-NHL subtypes.
Mosunetuzumab is a bispecific antibody targeting CD20 x CD3 re-directing T cells to target and destroy CD20-positive B cells. T-cell-based therapies including bispecific antibodies have revolutionized B-cell NHL treatment. Mosunetuzumab is approved for follicular lymphoma with at least 2 prior lines of therapy. There are also NCCN recommendations for its use in diffuse large B-cell lymphoma and in combination with polatuzumab vedotin in relapsed/refractory mantle cell lymphoma with prior BTK inhibitor therapy. Published trials show low rates of severe CRS and support outpatient administration in appropriate settings. Utilizing a search of PubMed, conference abstracts, and clinicaltrials.gov between 2020 and 2026, prospective trial data as well as retrospective real-world evidence and ongoing studies were included for a more complete picture of available data. This review summarizes the molecular design, mechanism of action, clinical efficacy, and safety of mosunetuzumab, an agent representative of immunotherapeutic advancement in lymphoma.
2026-07-28 | Peptide-Drug Conjugates for Targeted Delivery in Hematological Malignancies: From Design Principles to Clinical Application.
Hematological malignancies account for over 1.3 million new cases and approximately 700,000 deaths annually. Despite advances in targeted therapies, immunotherapies, and antibody-drug conjugates, relapse, refractory disease, and acquired drug resistance remain critical challenges. Peptide-drug conjugates (PDCs) have emerged as a promising targeted delivery platform, combining peptide-mediated specificity with potent cytotoxic payloads. In this review, we summarized the fundamental design principles of PDCs, including targeting peptide selection, linker engineering, and payload optimization, with emphasis on the biological characteristics of hematological malignancies. We then examined current preclinical and clinical progress across multiple myeloma, acute myeloid leukemia, myelodysplastic syndromes, B-cell non-Hodgkin lymphoma, and chronic myeloid leukemia. We further discussed emerging strategies such as cathepsin B-responsive PROTAC-PDC hybrids, nanotechnology-assisted delivery, and artificial intelligence-guided molecular design. Finally, we addressed key translational challenges, including tumor heterogeneity, payload resistance, and pharmacokinetic constraints, and proposed future directions toward biomarker-driven precision PDC therapy for hematological malignancies.
2026-07-22 | Glofitamab in the sequential treatment of relapsed/refractory B-Cell lymphoma: a single-center real-world study.
Glofitamab is a bispecific antibody (BsAb), and has good efficacy in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL), especially in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). This study explored its sequential treatment strategies and efficacy in the real world, including rescue therapy after chimeric antigen receptor T cell (CAR-T) therapy failure, bridging CAR-T therapy and monotherapy. This was a single-center retrospective cohort analysis of 24 patients with clearly diagnosed relapsed/refractory B-cell lymphoma, including primary diffuse large B-cell lymphoma (DLBCL), diffuse large B-cell lymphoma with Richter transformation (DLBCL-RT), and Burkitt lymphoma (BL). Patients were divided into three groups according to the treatment sequence: Group 1 (Glofitamab rescue therapy after progression of CAR-T therapy), group 2 (Glofitamab bridging subsequent CAR-T therapy), and group 3 (Glofitamab monotherapy), who received Glofitamab at our center between September 2024 and December 2025. In the single-center real-world experience, Glofitamab demonstrated controllable safety and durable anti-tumor activity in three clinical scenarios. Especially, it could still bring clinical benefits even after CAR-T therapy failed, and it explored the sequential treatment strategy of Glofitamab and CAR-T.
2026-08-15 | SOHO State of the Art Updates and Next Questions| Mediastinal Gray-zone Lymphoma: Novel Biologic Insights and Updates on How Best to Approach This Rare Entity.
Mediastinal gray zone lymphoma (MGZL) is a very rare aggressive B-cell non-Hodgkin lymphoma characterized by clinical, pathologic, and molecular features that overlap between nodular sclerosis Hodgkin lymphoma (NSHL) and primary mediastinal B-cell lymphoma (PMBL). While these are clinically related lymphomas, recent molecular profiling studies demonstrated similarities between these 3 entities, including alterations in the nuclear factor-κB pathway, JAK2/STAT signaling, copy number alterations in 9p24.1, and immune evasion. In the most recent WHO-5 and ICC classifications, the definition of GZL was restricted to mediastinal GZL (MGZL), which remains as a separate entity between NSHL and PMBL; however, non-mediastinal GZL was classified under diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS). Given the rarity of the disease, evolving definition, and diagnostic challenges, few prospective studies have been undertaken to evaluate treatment outcomes. Response rates and survival with frontline chemotherapy are inferior compared to PMBL, and retrospective studies suggest superiority of dose-intensive regimens compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in MGZL. Despite recent therapeutic advancements in PMBL and classical Hodgkin lymphoma (cHL), most clinical trials have excluded patients with MGZL, leading to uncertainty regarding the best therapeutic strategy in both the frontline and relapsed/refractory settings.
2026-08-13 | The Role of Direct-Acting Antivirals (DAAs) in Hepatitis C Virus-Associated Lymphoproliferative Disorders.
Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, affecting approximately 50 million people worldwide. An estimated 15-30% of individuals with chronic HCV infection progress to cirrhosis, which may subsequently develop into hepatocellular carcinoma. Beyond liver disease, HCV is associated with a broad spectrum of extrahepatic manifestations, particularly mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). Persistent viral infection induces chronic antigenic stimulation of B lymphocytes, a key pathogenic mechanism underlying the progression from MC to overt B-NHL. These observations have important therapeutic implications and support the use of antiviral therapy as a cornerstone of treatment. The efficacy of direct-acting antivirals (DAAs) has been well established in patients with HCV-related MC and cryoglobulinemic vasculitis. Several studies have shown that DAAs achieve sustained virologic response rates exceeding 90%, often approaching 100% in contemporary cohorts. Viral eradication is frequently associated with clinical and immunological improvement, as well as regression of cryoglobulinemia. Encouraging outcomes have also been reported in patients with HCV-associated indolent B-NHL, particularly marginal zone lymphoma, although confirmation in larger studies with longer follow-up is needed. In patients with HCV-positive aggressive lymphomas, DAAs have been safely administered in combination with immunochemotherapy, yielding promising results. This review summarizes the current evidence on HCV-associated MC and B-NHL and discusses the impact of DAA therapy on the clinical course and management of these disorders.
2026-07-31 | Mosunetuzumab: A bispecific CD20 × CD3 antibody for follicular lymphoma with promising evidence in other B-NHL subtypes.
Mosunetuzumab is a bispecific antibody targeting CD20 x CD3 re-directing T cells to target and destroy CD20-positive B cells. T-cell-based therapies including bispecific antibodies have revolutionized B-cell NHL treatment. Mosunetuzumab is approved for follicular lymphoma with at least 2 prior lines of therapy. There are also NCCN recommendations for its use in diffuse large B-cell lymphoma and in combination with polatuzumab vedotin in relapsed/refractory mantle cell lymphoma with prior BTK inhibitor therapy. Published trials show low rates of severe CRS and support outpatient administration in appropriate settings. Utilizing a search of PubMed, conference abstracts, and clinicaltrials.gov between 2020 and 2026, prospective trial data as well as retrospective real-world evidence and ongoing studies were included for a more complete picture of available data. This review summarizes the molecular design, mechanism of action, clinical efficacy, and safety of mosunetuzumab, an agent representative of immunotherapeutic advancement in lymphoma.
2026-07-28 | Peptide-Drug Conjugates for Targeted Delivery in Hematological Malignancies: From Design Principles to Clinical Application.
Hematological malignancies account for over 1.3 million new cases and approximately 700,000 deaths annually. Despite advances in targeted therapies, immunotherapies, and antibody-drug conjugates, relapse, refractory disease, and acquired drug resistance remain critical challenges. Peptide-drug conjugates (PDCs) have emerged as a promising targeted delivery platform, combining peptide-mediated specificity with potent cytotoxic payloads. In this review, we summarized the fundamental design principles of PDCs, including targeting peptide selection, linker engineering, and payload optimization, with emphasis on the biological characteristics of hematological malignancies. We then examined current preclinical and clinical progress across multiple myeloma, acute myeloid leukemia, myelodysplastic syndromes, B-cell non-Hodgkin lymphoma, and chronic myeloid leukemia. We further discussed emerging strategies such as cathepsin B-responsive PROTAC-PDC hybrids, nanotechnology-assisted delivery, and artificial intelligence-guided molecular design. Finally, we addressed key translational challenges, including tumor heterogeneity, payload resistance, and pharmacokinetic constraints, and proposed future directions toward biomarker-driven precision PDC therapy for hematological malignancies.
2026-07-22 | Glofitamab in the sequential treatment of relapsed/refractory B-Cell lymphoma: a single-center real-world study.
Glofitamab is a bispecific antibody (BsAb), and has good efficacy in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL), especially in relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). This study explored its sequential treatment strategies and efficacy in the real world, including rescue therapy after chimeric antigen receptor T cell (CAR-T) therapy failure, bridging CAR-T therapy and monotherapy. This was a single-center retrospective cohort analysis of 24 patients with clearly diagnosed relapsed/refractory B-cell lymphoma, including primary diffuse large B-cell lymphoma (DLBCL), diffuse large B-cell lymphoma with Richter transformation (DLBCL-RT), and Burkitt lymphoma (BL). Patients were divided into three groups according to the treatment sequence: Group 1 (Glofitamab rescue therapy after progression of CAR-T therapy), group 2 (Glofitamab bridging subsequent CAR-T therapy), and group 3 (Glofitamab monotherapy), who received Glofitamab at our center between September 2024 and December 2025. In the single-center real-world experience, Glofitamab demonstrated controllable safety and durable anti-tumor activity in three clinical scenarios. Especially, it could still bring clinical benefits even after CAR-T therapy failed, and it explored the sequential treatment strategy of Glofitamab and CAR-T.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
7 orphan drug designations for B-cell non-Hodgkin lymphoma, including 3 approved therapies.
7 orphan drug designations for B-cell non-Hodgkin lymphoma, including 3 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Hu1D10, humanized monoclonal antibody | antibodies | FDA | 2001-11-28 | — | PDL BioPharma, Inc. |
Murine MAb (Lym-1) and Iodine 131-I radiolabeled murine MAb (Lym-1) to human B-cell lymphoma | antibodies | FDA | 1998-11-27 | — | Peregrine Pharmaceuticals, Inc. |
ibritumomab tiuxetan [Zevalin] | antibodies | FDA | 1994-09-06 | 2002-02-19 | Acrotech Biopharma LLC |
rituximab [Rituxan] | antibodies | FDA | 1994-06-13 | 1997-11-26 | Genentech, Inc. |
Tositumomab and iodine I 131 tositumomab [Bexxar] | antibodies | FDA | 1994-05-16 | 2003-06-27 | GlaxoSmithKline LLC |
Iodine I 131 Lym-1 Monoclonal Antibody | antibodies | FDA | 1987-11-02 | — | Lederle Laboratories Division |
Monoclonal antibodies (murine or human) to B-cell lymphoma | antibodies | FDA | 1986-05-06 | — | IDEC Pharmaceuticals Corporation |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.