Study design and population

This was a phase 2 single-arm, open-label study. The inclusion criteria were histologically confirmed diagnosis of classical Hodgkin lymphoma, relapsed or refractory after at least 2 previous lines of therapy, age 18 to 70 years old, no uncontrolled bacterial or fungal infection at the time of enrolment, no requirement for intensive care, pregnancy, active or prior documented autoimmune diseases requiring systemic treatment. Patients who had received previous therapy with nivolumab or other PD-1 inhibitor were excluded from the study. This study was performed in accordance with the Declaration of Helsinki and approved by the institutional review board. All enrolled patients gave written informed consent. The patients received IV nivolumab infusions at a fixed dose of 40 mg on day 1 of a 14-day cycle up to 24 cycles in the absence of tumor progression or treatment intolerance. The dose was chosen because it is a minimal pharmaceutical form currently produced, exceeding the dose of 0.3 mg/kg that was shown to saturate peripheral PD-1 receptors in PK studies.¹² The study design did not restrict the therapy of patients after the end of study treatment or after disease progression at discretion of treating physician. The disease status was assessed every 3 months during the first 2 years, then every 6 months, or earlier in special circumstances (alloHSCT, or initiation of another treatment regimens). The response was assessed by investigators, using PET/CT scans and according to the Lymphoma Response to Immunomodulatory therapy Criteria (LYRIC). Adverse events (AEs) were monitored from baseline through the End-of-Treatment visit and graded according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03.

Primary chemoresistance was defined either by progression at any time during first-line therapy and up to 3 months after the end of treatment, and/or by persistence of a PET positive residual mass, using the quantitative 5-point scale Deauville score. Early relapse was defined as time to treatment failure more than three months but less than 12 months after end of first-line therapy.