Patients can be consented and registered at any time before, during or within 14 days after completing two cycles of first line or second line salvage therapy (4 cycles if being treated with brentuximab vedotin).

A PET-CT scan will be performed under trial conditions following 2 cycles of first line or second salvage (4 cycles if being treated with brentuximab vedotin) to determine eligibility for trial treatment.

• Patients who are PET-negative (Deauville 1-3) will not be eligible for trial treatment.They will enter follow up for the purpose of the trial, and any further treatment will be at their treating clinician’s discretion.

• Patients who are PET-positive (Deauville 4-5) after first line salvage chemotherapy will receive 4 x 14-day cycles of nivolumab.

  A further PET-CT scan will then be performed:

• Patients who are PET negative (Deauville 1-3) will stop trial treatment and enter followup.

Inclusion criteria for registration

• Age 16 or over

• Primary refractory classical Hodgkin lymphoma or classical Hodgkin lymphoma in firstrelapse

• About to receive, receiving or within 14 days of first 2 cycles of first or second line salvage therapy (4 cycles if receiving treatment with brentuximab vedotin)

• Fit for autologous stem cell transplantation

• Written informed consent

• Willing to comply with the contraceptive requirements of the trial

  Exclusion criteria for registration

• Nodular lymphocyte predominant Hodgkin lymphoma

• Women who are pregnant or breastfeeding

• History of colitis, inflammatory bowel disease or pneumonitis

• Patients with autoimmune disorders excluding patients with vitiligo, diabetes mellitustype 1, hypo- and hyperthyroidism not requiring immunosuppressive therapy

• Known active hepatitis B or C infection

• Known HIV infection

• History of allergy (including severe/life threatening skin reaction) to monoclonalantibodies, anaphylaxis or uncontrolled allergy

• Major surgery within 4 weeks prior to registration

• Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within the past 6 months

• Non-haematological malignancy within the past 3 years (some exceptions apply – see trial protocol)

  Inclusion criteria – trial treatment

• Has received 2 cycles of first line or second line salvage chemotherapy (4 cycles ifbeing treated with brentuximab vedotin)

• PET positive (Deauville score 4 or 5) after 2 cycles of first or second line salvage chemotherapy (4 cycles if being treated with brentuximab vedotin)

• Fit for further salvage chemotherapy

• ECOG performance status 0-1

• Creatinine clearance >30ml/min calculated by Cockroft-Gault formula

• Bilirubin

• Adequate bone marrow function (Hb >80g/l, Platelets >50 x 10⁹/l,neutrophils >1.0 x 10⁹/l

  Exclusion criteria for trial treatment

• Deauville score 1-3 after 2 cycles of first or second line salvage chemotherapy (4 cycles if being treated with brentuximab vedotin)

• Positive serology for hepatitis B or C (some exceptions apply – see trial protocol)

• Active infection requiring systemic therapy

• Ongoing immunosuppressive therapy, apart from inhaled, intranasal, topical corticosteroids or systemic corticosteroids at low doses (≤10mg prednisolone or equivalent per day).

• Chemo-or radiotherapy or corticosteroids at a dose of more than 10mg/day prednisolone or equivalent within 14 days prior to response PET-CT. NOTE: corticosteroids can be used AFTER a positive PET-CT scan for symptomatic disease but must be weaned to a dose of prednisolone ≤10mg/day or less (or equivalent) at least 7 days prior to starting nivolumab.

• Treatment with any investigational agent within 28 days prior to planned start of nivolumab

• Ongoing grade 2-4 non-haematological toxicities related to prior Hodgkin lymphoma treatments, with the exception of alopecia and grade 2 fatigue

• Pregnant or breastfeeding women