This is a single-center, open-label, phase 2 pilot study evaluating the efficacy and safety of a response-adapted first-line treatment strategy for patients with classical Hodgkin lymphoma (cHL) and unfavorable prognostic factors. The FINISH protocol (First-line Immuno-chemotherapy Navigated by Interim PET for Stratification and Hazard minimization In Hodgkin lymphoma) integrates nivolumab into induction therapy and tailors subsequent treatment based on interim PET-CT response. The study also includes exploratory monitoring of circulating tumor DNA (ctDNA) to investigate its role in early response assessment and residual disease detection.

The FINISH study (First-line Immuno-chemotherapy Navigated by Interim PET for Stratification and Hazard minimization In Hodgkin lymphoma) is designed to evaluate a novel personalized treatment strategy for newly diagnosed patients with classical Hodgkin lymphoma (cHL) and advanced-stage or bulky disease. All participants receive initial immunochemotherapy with nivolumab plus EACOPD-14. Treatment is then adapted based on interim PET-CT after two cycles. Patients with a complete metabolic response (Deauville score 1-3) receive de-escalated consolidation with Nivo-AVD followed by nivolumab monotherapy. Patients with inadequate metabolic response undergo continued or intensified therapy based on further PET response.

In addition to clinical and imaging-based endpoints, the study incorporates exploratory monitoring of circulating tumor DNA (ctDNA) at predefined time points. This includes analysis of ctDNA kinetics and correlation with PET response, aiming to develop a molecular framework for response stratification and early detection of residual disease.

The primary goal is to increase treatment efficacy while minimizing long-term toxicity through PET-guided de-escalation and early immunotherapy integration. Safety, feasibility, and molecular response patterns will be analyzed to inform future trials.

Inclusion Criteria:

• Signed written informed consent prior to any study-specific procedures
• Histologically confirmed classical Hodgkin lymphoma (cHL)
• Newly diagnosed disease, Ann Arbor stage IIB (bulky), III, or IV
• At least one measurable lesion ≥15 mm in the longest diameter (by CT)
• Age between 18 and 60 years (inclusive)
• ECOG performance status 0-2
• PET-CT performed at baseline
• No prior chemotherapy, radiotherapy, or immunotherapy for lymphoma
• Adequate organ function, including:
• Serum creatinine ≤ 0.2 mmol/L
• Absence of severe cardiac, pulmonary, hepatic, or renal dysfunction
• Ability to comply with the study protocol and scheduled visits

Exclusion Criteria:

• Active hepatitis B or C infection
• Positive test for HIV
• Pregnancy or breastfeeding
• Prior or active autoimmune disease requiring systemic therapy
• Vaccination with a live vaccine within 30 days prior to first nivolumab dose
• History of non-infectious pneumonitis requiring corticosteroids
• Prior malignancy (except for adequately treated basal cell carcinoma or cervical carcinoma in situ)
• Congestive heart failure, unstable angina, recent myocardial infarction, or severe cardiac arrhythmias
• Severe renal impairment (serum creatinine > 0.2 mmol/L), unless lymphoma-related
• Severe hepatic dysfunction, unless directly related to lymphoma
• Severe pneumonia with respiratory failure or hypoxemia not corrected within 2-3 days
• Sepsis or hemodynamic instability
• Life-threatening bleeding events (e.g., gastrointestinal or cerebral hemorrhage)
• Cachexia (total serum protein < 35 g/L), unless due to lymphoma-related liver damage
• Decompensated diabetes mellitus
• Any somatic or psychiatric condition that, in the investigator's judgment, precludes informed consent or study participation