RARE DISEASE
Classic Hodgkin lymphoma
Classic Hodgkin lymphoma
Classic Hodgkin lymphoma
Synonyms: Classic Hodgkin disease
Synonyms: Classic Hodgkin disease
Synonyms: Classic Hodgkin disease
Drug discovery
6
drugs
With orphan designations
Overview
Classic Hodgkin lymphoma (cHL) is a B-cell malignancy characterized by Hodgkin-Reed-Sternberg cells within an inflammatory microenvironment. It exhibits bimodal age distribution and high curability (85-90% 5-year survival) with modern therapies [1][6][15]. First-line treatment combines chemotherapy (ABVD, BEACOPP) with response-adapted radiotherapy [3][5][13], while relapsed/refractory cases utilize salvage regimens, immunotherapy (PD-1 inhibitors), and stem cell transplantation [3][8][13].
Population
Bimodal incidence: peaks at 20-34 years (31.2% of cases) and >55 years [2][12]
Male predominance (M:F ≈ 1.4:1), higher incidence in high-income countries (2.8/100k vs 0.44/100k) [2][12][7]
Disparities: Hispanic patients present younger (mean 38 vs 41 years) with higher uninsured rates (15% vs 6%) [7]
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
1,339 drug discovery papers about Classic Hodgkin lymphoma, with 2 first-in-class and 14 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,339 drug discovery papers about Classic Hodgkin lymphoma, with 2 first-in-class and 14 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-10 | Long-term follow-up of PET/CT-adapted therapy after three cycles of ABVD for all stages of classic Hodgkin lymphoma: Results of the GATLA LH-05 trial.
The Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) LH-05 trial evaluated positron emission tomography-computed tomography (PET-CT)-guided ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in patients with stage I-IV classic Hodgkin lymphoma (cHL). A total of 563 patients with cHL stages I-IV were included in the prospective, non-randomized GATLA LH-05 trial. Patients received three cycles of ABVD followed by PET-CT (PET3). Patients with PET3 Deauville score (DS) 1-2 discontinued treatment, DS 3-4 completed six ABVD with involved-field radiotherapy (IFRT) and DS 5 received salvage chemotherapy. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic factors for PFS were assessed using Cox regression. After a median follow-up of 93.5 months Interquartile Range (IQR) 54-139, 5- and 10-year PFS for the whole cohort were 78.9% 95% Confidence Interval (CI) 75.5-82.6 and 76.2% (95% CI 72.4-80.2) respectively. Five- and 10-year OS were 95.2% (95% CI 93.3-97.0) and 93.7% (95% CI 91.5-96.0). All PET3-negative patients achieved 10-year PFS of 84.4%. PET3 was the strongest predictor of PFS, while disease stage had no independent prognostic significance. With extended follow-up, PET-CT-adapted therapy after three cycles of ABVD provides durable disease control while reducing exposure to chemotherapy and radiotherapy. These results support PET-CT-guided treatment discontinuation in PET3-negative patients across all stages of cHL.
2026-08-03 | [Recent advances and future perspectives in the treatment of classical Hodgkin lymphoma].
Classical Hodgkin lymphoma (cHL) is a highly curable malignancy, with long-term remission achieved in approximately 85% of patients with limited-stage disease and in about 70% of those with advanced-stage disease following first-line therapy. In limited-stage cHL, treatment is generally guided by appropriate risk stratification, and the combination of ABVD followed by radiotherapy has long constituted the therapeutic backbone. For advanced-stage disease, six cycles of brentuximab vedotin plus AVD (BV-AVD) are currently regarded as the standard first-line treatment, whereas six cycles of ABVD remains a reasonable option for older patients in whom treatment tolerability is a particular concern. In recent years, the results of large-scale clinical trials evaluating first-line regimens incorporating brentuximab vedotin (BV) or immune checkpoint inhibitors (IO), together with interim PET-adapted treatment strategies, have shown promise for further improving treatment outcomes while minimizing the use of radiotherapy. For relapsed or refractory disease, immunotherapeutic approaches, including CD30-directed CAR T-cell therapy, are under active development. In parallel, circulating tumor DNA (ctDNA) is emerging as a promising biomarker for minimal residual disease assessment, and ctDNA-based molecular classification has also been proposed. This review outlines the current status and unresolved challenges of first-line treatment for cHL and discusses future perspectives in this evolving field.
2026-07-31 | Haematopoietic cell transplantation for relapsed or refractory classical Hodgkin lymphoma: a retrospective, registry-based cohort study of 19 498 patients from the EBMT Lymphoma Working Group.
Autologous haematopoietic cell transplantation (auto-HCT) is the recommended treatment for chemosensitive relapsed Hodgkin lymphoma, while allogeneic haematopoietic cell transplantation (allo-HCT) is indicated for patients who had unsuccessful auto-HCT. The introduction of novel therapeutic agents, alongside advances in donor selection, conditioning regimens, and graft-versus-host disease prophylaxis, might improve post-transplantation outcomes, however supporting data remain limited. We aimed to evaluate changes in post-transplantation outcomes over the period 2010-22, and to identify predictors of these outcomes. We conducted a retrospective, registry-based cohort study of patients aged 18 years or older with relapsed or refractory classical Hodgkin lymphoma undergoing first auto-HCT or first allo-HCT between Jan 1, 2010, and Dec 31, 2022, registered with the European Society for Blood and Marrow Transplantation (EBMT), with data from more than 600 transplantation centres, across 53 countries, reporting all HCTs and yearly follow-ups. Patients who received allo-HCT for relapse after auto-HCT were included but tandem transplantations were excluded. For allo-HCT, we included patients who received grafts from matched related donors, mismatched related donors, and unrelated donors. The primary endpoints were overall survival and progression-free survival, which were assessed with the Kaplan-Meier method at 2 years and 5 years after HCT. Multivariate analyses were performed using the Cox proportional-hazards regression model to identify predictive factors. We identified 22 047 patients who received a first transplantation for relapsed or refractory Hodgkin lymphoma, after excluding 1324 patients with missing follow-up data and 1225 patients with nodular lymphocyte predominant Hodgkin lymphoma, 19 498 patients were retained: 15 648 received auto-HCT (6772 [43%] were female and 8839 [57%] were male, data were missing for 37 patients); median age at HCT was 35 years [IQR 27-47]; median follow-up was 2·4 years [IQR 2·3-2·5]), and 3850 received allo-HCT (1572 [41%] female and 2273 [59%] were male, data were missing for five patients; median age at HCT 32 years [IQR 26-42]; median follow-up was 3·9 years [IQR 3·8-4·1]). For auto-HCT, from years 2010-14 to years 2019-22, the 2-year progression-free survival increased from 63% (95% CI 62-65) to 73% (71-74) and overall survival increased from 85% (95% CI 84-86) to 93% (91-94). Partial response (hazard ratio [HR] 1·92 [95% CI 1·74-2·11]) or stable or progressive disease (2·45 [2·17-2·76]) at transplantation negatively affected progression-free survival. For allo-HCT, from years 2010-14 to years 2019-22, the 2-year progression-free survival, and overall survival, increased from 44% (95% CI 41-46) to 62% (58-66), and from 66% (63-68) to 72% (68-75), respectively. Partial response (HR 1·58 [95% CI 1·39-1·78]) or stable/progressive disease (2·28 [2·02-2·58]) at transplantation negatively affected progression-free survival. To our knowledge, this is the largest study on HCT for Hodgkin lymphoma in recent years, and our findings that outcomes after auto-HCT and allo-HCT improved over time provide relevant information that could set the basis for prospective trials or additional studies. None.
2026-07-30 | Impact of EBV Status and Histology on Patient Outcomes with Nivolumab-AVD vs BV-AVD in Advanced Classic Hodgkin Lymphoma (S1826).
Classic Hodgkin lymphoma (cHL) associated with Epstein-Barr virus (EBV) positivity as well as non-nodular sclerosis (non-NS) histologic subtypes have demonstrated poorer outcomes compared to EBV-negative and nodular sclerosis cases. We report a prespecified subset analysis of patients enrolled in the phase III SWOG S1826 trial to evaluate outcomes based on EBV status and histologic subtype in patients treated with nivolumab-AVD (N-AVD) or brentuximab vedotin (BV)-AVD. In the phase III SWOG S1826 trial, patients with stage III-IV cHL were randomized to N-AVD or BV-AVD. Of 970 eligible patients, 522 had known EBV status. N-AVD improved 3-year progression-free survival (PFS) in EBV-positive (91% v 70%; HR, 0.30; P = 0.01) and EBV-negative patients (90% v 84%; HR, 0.64; P = 0.09). Among 664 patients with slides available for histology review, 102 (15.4%) had non-NS subtypes. N-AVD prolonged 3-year PFS in patients with non-NS (86% v 63%; HR, 0.33; P = 0.006) and NS histologic subtype (93% v 86%; HR, 0.53; P = 0.01). Non-NS histology independently was associated with inferior outcomes (HR, 2.54; P < 0.0001) after adjusting for treatment in the entire cohort. However, N-AVD treatment still had favorable PFS within this high-risk group. In addition, patients with EBV positivity or non-NS histology cHL treated with BV-AVD had significantly worse PFS (HR, 1.97; P = 0.03 for EBV; and HR, 3.08; P < 0.0001 for histology). N-AVD substantially abrogated the historically poor prognosis associated with EBV positivity and non-NS histology in advanced-stage cHL. These results support N-AVD as frontline standard of care, particularly in high-risk biologic subgroups. (NCT03907488).
2026-07-28 | Frontline ABVD Remains an Effective Option in Advanced-Stage Classical Hodgkin Lymphoma: Real-World Data from Turkey.
Objectives: Novel agents such as brentuximab vedotin and anti-PD-1 antibodies, together with PET-adapted intensified strategies, have improved outcomes in advanced-stage classical Hodgkin lymphoma (cHL). However, their applicability remains limited in many middle-income countries because of restricted drug availability, reimbursement barriers, and toxicity concerns. Therefore, real-world data on the effectiveness of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) remains essential. Methods: We conducted a retrospective two-center study including 95 patients with newly diagnosed cHL treated with first-line ABVD. Baseline characteristics, treatment response, progression-free survival (PFS), overall survival (OS), and mortality were compared between early-stage (I-II, n = 33) and advanced-stage (III-IV, n = 62) disease. Results: The median age was 38 years (range, 18-73), and 69.5% were male; 65% had advanced-stage. Complete response rates were high in both early-stage (97%) and advanced-stage (95.2%) patients. Median PFS (21 vs. 23 months; p = 0.994) and OS (23 vs. 25 months; p = 0.848) were similar. Five-year OS was 84.3% for early-stage and 98% for advanced-stage patients (p = 0.292), while five-year PFS was 55.3% and 29.6% (p = 0.526). Mortality rates were comparable. Conclusions: In this real-world cohort, first-line ABVD achieved high response rates and favorable long-term survival in advanced-stage cHL, supporting its continued use as a frontline treatment option, particularly in settings where access to novel therapies may be limited.
2026-08-10 | Long-term follow-up of PET/CT-adapted therapy after three cycles of ABVD for all stages of classic Hodgkin lymphoma: Results of the GATLA LH-05 trial.
The Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) LH-05 trial evaluated positron emission tomography-computed tomography (PET-CT)-guided ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in patients with stage I-IV classic Hodgkin lymphoma (cHL). A total of 563 patients with cHL stages I-IV were included in the prospective, non-randomized GATLA LH-05 trial. Patients received three cycles of ABVD followed by PET-CT (PET3). Patients with PET3 Deauville score (DS) 1-2 discontinued treatment, DS 3-4 completed six ABVD with involved-field radiotherapy (IFRT) and DS 5 received salvage chemotherapy. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic factors for PFS were assessed using Cox regression. After a median follow-up of 93.5 months Interquartile Range (IQR) 54-139, 5- and 10-year PFS for the whole cohort were 78.9% 95% Confidence Interval (CI) 75.5-82.6 and 76.2% (95% CI 72.4-80.2) respectively. Five- and 10-year OS were 95.2% (95% CI 93.3-97.0) and 93.7% (95% CI 91.5-96.0). All PET3-negative patients achieved 10-year PFS of 84.4%. PET3 was the strongest predictor of PFS, while disease stage had no independent prognostic significance. With extended follow-up, PET-CT-adapted therapy after three cycles of ABVD provides durable disease control while reducing exposure to chemotherapy and radiotherapy. These results support PET-CT-guided treatment discontinuation in PET3-negative patients across all stages of cHL.
2026-08-03 | [Recent advances and future perspectives in the treatment of classical Hodgkin lymphoma].
Classical Hodgkin lymphoma (cHL) is a highly curable malignancy, with long-term remission achieved in approximately 85% of patients with limited-stage disease and in about 70% of those with advanced-stage disease following first-line therapy. In limited-stage cHL, treatment is generally guided by appropriate risk stratification, and the combination of ABVD followed by radiotherapy has long constituted the therapeutic backbone. For advanced-stage disease, six cycles of brentuximab vedotin plus AVD (BV-AVD) are currently regarded as the standard first-line treatment, whereas six cycles of ABVD remains a reasonable option for older patients in whom treatment tolerability is a particular concern. In recent years, the results of large-scale clinical trials evaluating first-line regimens incorporating brentuximab vedotin (BV) or immune checkpoint inhibitors (IO), together with interim PET-adapted treatment strategies, have shown promise for further improving treatment outcomes while minimizing the use of radiotherapy. For relapsed or refractory disease, immunotherapeutic approaches, including CD30-directed CAR T-cell therapy, are under active development. In parallel, circulating tumor DNA (ctDNA) is emerging as a promising biomarker for minimal residual disease assessment, and ctDNA-based molecular classification has also been proposed. This review outlines the current status and unresolved challenges of first-line treatment for cHL and discusses future perspectives in this evolving field.
2026-07-31 | Haematopoietic cell transplantation for relapsed or refractory classical Hodgkin lymphoma: a retrospective, registry-based cohort study of 19 498 patients from the EBMT Lymphoma Working Group.
Autologous haematopoietic cell transplantation (auto-HCT) is the recommended treatment for chemosensitive relapsed Hodgkin lymphoma, while allogeneic haematopoietic cell transplantation (allo-HCT) is indicated for patients who had unsuccessful auto-HCT. The introduction of novel therapeutic agents, alongside advances in donor selection, conditioning regimens, and graft-versus-host disease prophylaxis, might improve post-transplantation outcomes, however supporting data remain limited. We aimed to evaluate changes in post-transplantation outcomes over the period 2010-22, and to identify predictors of these outcomes. We conducted a retrospective, registry-based cohort study of patients aged 18 years or older with relapsed or refractory classical Hodgkin lymphoma undergoing first auto-HCT or first allo-HCT between Jan 1, 2010, and Dec 31, 2022, registered with the European Society for Blood and Marrow Transplantation (EBMT), with data from more than 600 transplantation centres, across 53 countries, reporting all HCTs and yearly follow-ups. Patients who received allo-HCT for relapse after auto-HCT were included but tandem transplantations were excluded. For allo-HCT, we included patients who received grafts from matched related donors, mismatched related donors, and unrelated donors. The primary endpoints were overall survival and progression-free survival, which were assessed with the Kaplan-Meier method at 2 years and 5 years after HCT. Multivariate analyses were performed using the Cox proportional-hazards regression model to identify predictive factors. We identified 22 047 patients who received a first transplantation for relapsed or refractory Hodgkin lymphoma, after excluding 1324 patients with missing follow-up data and 1225 patients with nodular lymphocyte predominant Hodgkin lymphoma, 19 498 patients were retained: 15 648 received auto-HCT (6772 [43%] were female and 8839 [57%] were male, data were missing for 37 patients); median age at HCT was 35 years [IQR 27-47]; median follow-up was 2·4 years [IQR 2·3-2·5]), and 3850 received allo-HCT (1572 [41%] female and 2273 [59%] were male, data were missing for five patients; median age at HCT 32 years [IQR 26-42]; median follow-up was 3·9 years [IQR 3·8-4·1]). For auto-HCT, from years 2010-14 to years 2019-22, the 2-year progression-free survival increased from 63% (95% CI 62-65) to 73% (71-74) and overall survival increased from 85% (95% CI 84-86) to 93% (91-94). Partial response (hazard ratio [HR] 1·92 [95% CI 1·74-2·11]) or stable or progressive disease (2·45 [2·17-2·76]) at transplantation negatively affected progression-free survival. For allo-HCT, from years 2010-14 to years 2019-22, the 2-year progression-free survival, and overall survival, increased from 44% (95% CI 41-46) to 62% (58-66), and from 66% (63-68) to 72% (68-75), respectively. Partial response (HR 1·58 [95% CI 1·39-1·78]) or stable/progressive disease (2·28 [2·02-2·58]) at transplantation negatively affected progression-free survival. To our knowledge, this is the largest study on HCT for Hodgkin lymphoma in recent years, and our findings that outcomes after auto-HCT and allo-HCT improved over time provide relevant information that could set the basis for prospective trials or additional studies. None.
2026-07-30 | Impact of EBV Status and Histology on Patient Outcomes with Nivolumab-AVD vs BV-AVD in Advanced Classic Hodgkin Lymphoma (S1826).
Classic Hodgkin lymphoma (cHL) associated with Epstein-Barr virus (EBV) positivity as well as non-nodular sclerosis (non-NS) histologic subtypes have demonstrated poorer outcomes compared to EBV-negative and nodular sclerosis cases. We report a prespecified subset analysis of patients enrolled in the phase III SWOG S1826 trial to evaluate outcomes based on EBV status and histologic subtype in patients treated with nivolumab-AVD (N-AVD) or brentuximab vedotin (BV)-AVD. In the phase III SWOG S1826 trial, patients with stage III-IV cHL were randomized to N-AVD or BV-AVD. Of 970 eligible patients, 522 had known EBV status. N-AVD improved 3-year progression-free survival (PFS) in EBV-positive (91% v 70%; HR, 0.30; P = 0.01) and EBV-negative patients (90% v 84%; HR, 0.64; P = 0.09). Among 664 patients with slides available for histology review, 102 (15.4%) had non-NS subtypes. N-AVD prolonged 3-year PFS in patients with non-NS (86% v 63%; HR, 0.33; P = 0.006) and NS histologic subtype (93% v 86%; HR, 0.53; P = 0.01). Non-NS histology independently was associated with inferior outcomes (HR, 2.54; P < 0.0001) after adjusting for treatment in the entire cohort. However, N-AVD treatment still had favorable PFS within this high-risk group. In addition, patients with EBV positivity or non-NS histology cHL treated with BV-AVD had significantly worse PFS (HR, 1.97; P = 0.03 for EBV; and HR, 3.08; P < 0.0001 for histology). N-AVD substantially abrogated the historically poor prognosis associated with EBV positivity and non-NS histology in advanced-stage cHL. These results support N-AVD as frontline standard of care, particularly in high-risk biologic subgroups. (NCT03907488).
2026-07-28 | Frontline ABVD Remains an Effective Option in Advanced-Stage Classical Hodgkin Lymphoma: Real-World Data from Turkey.
Objectives: Novel agents such as brentuximab vedotin and anti-PD-1 antibodies, together with PET-adapted intensified strategies, have improved outcomes in advanced-stage classical Hodgkin lymphoma (cHL). However, their applicability remains limited in many middle-income countries because of restricted drug availability, reimbursement barriers, and toxicity concerns. Therefore, real-world data on the effectiveness of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) remains essential. Methods: We conducted a retrospective two-center study including 95 patients with newly diagnosed cHL treated with first-line ABVD. Baseline characteristics, treatment response, progression-free survival (PFS), overall survival (OS), and mortality were compared between early-stage (I-II, n = 33) and advanced-stage (III-IV, n = 62) disease. Results: The median age was 38 years (range, 18-73), and 69.5% were male; 65% had advanced-stage. Complete response rates were high in both early-stage (97%) and advanced-stage (95.2%) patients. Median PFS (21 vs. 23 months; p = 0.994) and OS (23 vs. 25 months; p = 0.848) were similar. Five-year OS was 84.3% for early-stage and 98% for advanced-stage patients (p = 0.292), while five-year PFS was 55.3% and 29.6% (p = 0.526). Mortality rates were comparable. Conclusions: In this real-world cohort, first-line ABVD achieved high response rates and favorable long-term survival in advanced-stage cHL, supporting its continued use as a frontline treatment option, particularly in settings where access to novel therapies may be limited.
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Drug Discovery Landscape
6 orphan drug designations for Classic Hodgkin lymphoma.
6 orphan drug designations for Classic Hodgkin lymphoma.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Panobinostat [Faridak] | small molecules | EMA | 2010-02-02 | — | Novartis Europharm Limited |
Recombinant antibody construct against human CD30 and CD16A | antibodies | EMA | 2009-10-09 | — | Affimed GmbH |
Allogeneic umbilical cord blood cells-derived CD133+ cells ex vivo expanded [StemEX] | cell therapies | EMA | 2009-07-24 | — | Regulatory Resources Group Limited |
Brentuximab vedotin [Adcetris] | antibodies | EMA | 2009-01-15 | — | Takeda Pharma A/S |
Mocetinostat [MGDC0103] | small molecules | EMA | 2007-09-14 | — | ICON Clinical Research Limited |
Human IgG4 monoclonal antibody against HLA-DR | antibodies | EMA | 2005-06-16 | — | [INACTIVE] GPC Biotech AG |
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