Inclusion:
1. Newly diagnosed untreated classic Hodgkin lymphoma (Stage I-IV)
2. Age 60 years or over
3. In the view of the investigator, fit for combination chemotherapy (includes those who would require planned dose reduction although no lower than 50% doxorubicin)
4. Written informed consent
5. Measurable disease on contrast enhanced CT as defined by Cheson et al., 2014 1 (Nodal lesion of longest diameter 1.5 cm or extranodal lesion of longest diameter 1.0 cm).
6. FDG avid disease on baseline 18 FDG-PET-CT scan
7. ECOG performance status 0-2
8. Adequate bone marrow function (Platelets ≥75 x 109/L without platelet transfusion for 72 hours, Neutrophils ≥ 1.0 x 109/L without G-CSF for 7 days)
9. Adequate liver function tests (ALT / AST ≤2.5 x ULN, total serum bilirubin ≤ 1.5 x ULN)
10. Creatinine Clearance ≥ 30 ml/min as defined by the Cockroft-Gault equation
11. Adequate cardiac function as determined by a transthoracic echocardiogram or multiplanar gated radionuclide cardiac angiography (MUGA) demonstrating left ventricular ejection fraction is ≥ 50% and confirming the absence of severe valvular heart disease
12. Willing to comply with the contraceptive requirements of the trial
13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
Exclusion:
1. Nodular lymphocyte predominant Hodgkin lymphoma
2. History (within 2 years of registration) of active autoimmune disorders (with the exception of hypothyroidism, type 1 diabetes, vitiligo, alopecia)
3. History of solid organ transplant
4. Grade 2 or higher peripheral neuropathy
5. Presentation with disease causing symptomatic compression of vital structures (e.g. stridor due to tracheal compression). Other cases of radiological compression of
vital structures require discussion with TMG prior to registration
6. Women who are pregnant or breastfeeding
7. Active hepatitis B or C infection defined by Hepatitis B surface antigen positivity OR Anti-hepatitis B core antibody positivity with detectable circulating HBV, DNA (hepatitis B core antibody patients with undetectable circulating HBV DNA are eligible but must take suitable prophylaxis for reactivation), Anti-Hepatitis C antibody positivity unless patient has been treated for hepatitis C and has undetectable HCV RNA
8. Known HIV infection (unless controlled)
9. Positive PCR for SARS-CoV-2 RNA or lateral flow test for SARS-CoV2 within 1 week prior to registration. Patients with a history of SARS-CoV-2 infection within 4 weeks prior to
registration are required to have a subsequent documented negative PCR swab or lateral flow test.
10. Immunosuppressive therapy within the 2 months prior to registration apart from inhaled, intranasal or topical corticosteroids. Systemic corticosteroids are permitted prior to study entry but must be weaned to equal or less than 10 mg prednisolone / day for a minimum of 7 days prior to cycle 1 day 1
11. Live vaccine given within 30 days prior to registration
12. Active infection requiring systemic therapy with ongoing symptoms at registration or where the planned duration of therapy would continue beyond cycle 1 day 1
13. Major surgery within 4 weeks prior to registration (excisional biopsy is not considered major surgery)
14. Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within 6 months prior to registration
15. Previously treated haematological malignancy
16. Solid-organ malignancy active within the last 3 years, except where the natural history or treatment does not have the potential to interfere with assessment of safety or efficacy
of trial treatment, for example: Adequately treated non-melanoma skin cancer considered to be in remission, Melanoma in situ following resection, Carcinoma in situ of the breast or
cervix, Carcinoma of the prostate of Gleason grade 6 or less with stable prostate-specific antigen levels, Cancer considered cured by surgical resection or unlikely to impact survival
in the next 3 years, for example local transitional carcinoma of the bladder or benign tumours of the adrenal gland or pancreas. A history of other malignancies should be discussed with the trial management group prior to registration
17. Patient not fit for AVD chemotherapy in the opinion of the investigator