Hodgkin Lymphoma

Hodgkin lymphoma (HL) is a cancer of B-lymphocytes defined by the presence of a specific malignant cell — the Reed-Sternberg cell — which is large, often bi- or multi-nucleated, and surrounded by a distinctive reactive inflammatory infiltrate of normal lymphocytes, eosinophils, and other immune cells. This unique tumor biology makes HL biologically distinct from non-Hodgkin lymphomas (NHL), which are a heterogeneous group of over 60 different lymphoid malignancies without Reed-Sternberg cells.

The most clinically important difference is prognosis: Hodgkin lymphoma is one of the most curable cancers in oncology — approximately 80–90% of all patients achieve long-term disease-free survival with modern treatment. NHL is a much more diverse group, ranging from highly curable DLBCL to incurable but manageable indolent lymphomas, to aggressive T-cell lymphomas with poor outcomes. The treatment approaches also differ fundamentally — ABVD and BV-AVD are specific to HL, while NHL is treated with a wide range of subtype-specific regimens.

Hodgkin lymphoma is divided into two major entities. Classical Hodgkin lymphoma (cHL) accounts for approximately 95% of all HL cases and has four histologic subtypes based on the Reed-Sternberg cell background: nodular sclerosis (most common, ~65–70%), mixed cellularity (~20–25%), lymphocyte-rich (~5%), and lymphocyte-depleted (<5%). All classical HL subtypes are CD30-positive and CD15-positive, with negative or weak CD20.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for the remaining ~5% and is a biologically distinct disease. LP cells in NLPHL are CD20-positive and CD30-negative — the opposite of classical RS cells. This matters enormously because NLPHL is treated with rituximab-containing regimens (since rituximab targets CD20), while classical HL is treated with ABVD or BV-AVD (which lack rituximab). Treating NLPHL as if it were classical HL — without rituximab — is a management error. Correct subtype identification by an experienced hematopathologist is therefore essential before treatment begins.

First-line treatment depends on stage. For early-stage favorable HL (Stage I–II without adverse risk factors), the standard is ABVD for 2 cycles followed by involved-site radiotherapy (ISRT). For early-stage unfavorable HL, ABVD is extended to 4 cycles plus ISRT. For advanced-stage classical HL (Stage III–IV), BV-AVD — brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine — is now the preferred regimen for 6 cycles, having replaced ABVD as the preferred advanced-stage approach based on the ECHELON-1 trial demonstrating improved progression-free survival and elimination of bleomycin-related pulmonary toxicity.

The response to the first 2 cycles, assessed by interim PET-CT using the Deauville 5-point scale, guides whether treatment can be de-escalated or must be escalated. This PET-adapted approach is central to modern HL management and requires specialist lymphoma expertise to implement correctly.

The interim PET-CT, performed after 2 cycles of chemotherapy, is one of the most important tests in Hodgkin lymphoma management. It measures how well the lymphoma cells are responding to treatment by assessing whether they are still metabolically active on FDG-PET imaging. The result is reported using the Deauville 5-point scale: scores 1–2 indicate no residual metabolic activity; score 3 indicates activity equal to mediastinal blood pool (generally considered adequate response); scores 4–5 indicate activity moderately or markedly above the liver, signaling inadequate early response.

A negative interim PET (Deauville 1–3) means the treatment is working well — and in some protocols, this may allow de-escalation (such as omitting bleomycin from the remaining ABVD cycles based on the RATHL trial, or omitting radiotherapy in early-stage disease in selected patients). A positive interim PET (Deauville 4–5) means the disease is not responding adequately and usually prompts treatment escalation. Understanding your interim PET Deauville score and what it means for your specific treatment protocol is an important conversation to have with your lymphoma hematologist.

Brentuximab vedotin (BV) is an antibody-drug conjugate that combines a monoclonal antibody targeting CD30 — a protein strongly expressed on Reed-Sternberg cells in virtually all classical HL — with a potent cell-killing payload (MMAE). When BV binds to CD30 on an RS cell, the antibody-drug complex is internalized, the MMAE payload is released inside the cell, and the cell is killed. Because CD30 expression is near-universal in cHL and relatively restricted in normal tissues, BV delivers targeted cytotoxicity to HL cells with acceptable systemic toxicity.

Brentuximab vedotin has three approved roles in HL: first-line for advanced-stage cHL (in the BV-AVD combination), post-ASCT maintenance for high-risk patients (AETHERA trial, reducing relapse risk), and for relapsed/refractory cHL after ASCT or after two prior therapy lines. The main side effect is peripheral sensory neuropathy — tingling and numbness in the hands and feet — which is manageable with dose adjustments but requires close monitoring.

PD-1 inhibitors work by blocking the PD-1 protein on T-cells, which normally acts as a brake on T-cell activity when it binds to PD-L1 on tumor cells. In classical Hodgkin lymphoma, Reed-Sternberg cells have an extraordinarily high level of PD-L1 expression — caused by amplification of the 9p24.1 chromosomal region, which contains the PD-L1, PD-L2, and JAK2 genes. This makes RS cells unusually effective at suppressing T-cell attack. By blocking the PD-1 brake with pembrolizumab or nivolumab, the immune system is released to attack the RS cells — achieving response rates of 65–90% in relapsed/refractory cHL, which is among the highest seen with checkpoint inhibitors in any cancer type.

Both pembrolizumab and nivolumab are approved for relapsed/refractory cHL. They are also being investigated in combination with BV-AVD in first-line advanced-stage disease, where early results show very high complete metabolic response rates. For patients who have relapsed after ASCT or who are not ASCT candidates, PD-1 inhibitors represent the most active systemic treatment option currently available.

Relapse after first-line chemotherapy is managed with salvage therapy followed, in most transplant-eligible patients, by high-dose chemotherapy and autologous stem cell transplantation (ASCT). The first step is demonstrating that the disease still responds to treatment — salvage regimens including ICE, DHAP, or the increasingly preferred brentuximab vedotin plus nivolumab (a chemotherapy-free salvage combination with high PET-negativity rates) are used to achieve a complete metabolic response before ASCT.

After successful ASCT, brentuximab vedotin maintenance for up to 16 cycles significantly reduces the risk of further relapse in patients with high-risk features. For those who relapse after ASCT, pembrolizumab and nivolumab produce response rates of 65–70% and can bridge some patients to allogeneic stem cell transplantation. CD30-directed CAR-T cell therapy is being studied for patients who have failed both brentuximab vedotin and PD-1 inhibitor therapy. Specialist lymphoma center review at the time of relapse is strongly recommended — access to the full range of salvage options requires institution-specific expertise.

Hodgkin lymphoma survivors — many of whom are cured as young adults — face a meaningful long-term risk of treatment-related health consequences that emerge years to decades after completing therapy. The most important late effects are: cardiovascular disease (from mediastinal radiation and doxorubicin — including coronary artery disease, valvular disease, and heart failure); secondary cancers (breast cancer from mediastinal radiation in women treated before age 35, lung cancer, and therapy-related myeloid neoplasms from alkylating agents or topoisomerase inhibitors); pulmonary fibrosis (from bleomycin or mediastinal radiation); and hypothyroidism (from neck radiation).

Modern HL treatment has progressively minimized these risks through smaller radiation fields, lower radiation doses, elimination of bleomycin in BV-AVD, and PET-guided de-escalation strategies. However, patients treated with older regimens or mediastinal radiation face the highest long-term risks and require structured survivorship follow-up including cardiovascular monitoring, earlier breast cancer screening, and thyroid function checks. This survivorship care is a critical part of comprehensive HL management.

Yes. CancerFax supports Hodgkin lymphoma patients and families throughout the treatment process. We begin by reviewing your biopsy report and IHC panel to confirm the correct HL subtype (classical vs NLPHL, specific classical subtype), your PET-CT staging and interim response assessment (Deauville score), your IPS score if applicable, and your treatment history — to establish where you are in the disease course and which options are most relevant.

Based on this review, we identify which treatment approaches apply — from BV-AVD or ABVD and PET-guided adaptation for newly diagnosed disease, to pembrolizumab or nivolumab and ASCT planning for relapsed disease, to post-ASCT brentuximab vedotin maintenance eligibility, and to CD30-CAR-T programs at specialist centers in China and globally for multiply relapsed patients. We coordinate second opinion consultations with specialist lymphoma hematologists and facilitate international treatment navigation for patients seeking access to novel salvage programs, allogeneic transplant expertise, or clinical trial enrollment. Send your medical reports to get started.