Personalized immunotherapy with the checkpoint inhibitor tislelizumab for early-stage, high-risk classical Hodgkin lymphoma

Classical Hodgkin lymphoma (cHL) is a malignant disease of the lymphatic system in which lymphocytes—a type of white blood cell that is part of the immune system—become cancerous. The most common symptoms include swollen lymph nodes, fever, night sweats, weight loss, and itching. This type of cancer often affects young adults. The exact causes are unclear, but genetic factors and infections such as the Epstein-Barr virus (EBV) may play a role. Treatment depends on the stage and risk classification of the disease. The standard treatment for early-stage, high-risk cHL typically includes chemotherapy and/or radiation therapy. Since the disease usually responds very well to treatment, many clinical trials in recent years have focused on minimizing side effects by using less intensive treatment regimens and medications with better tolerability. Tislelizumab is a so-called PD-1 inhibitor (checkpoint inhibitor) that activates the immune system to fight cancer cells. To date, tislelizumab has not been approved for the treatment of cHL, but it is already being used for other types of cancer.

The goal of the INDIE study (Phase 2 study) is to investigate the efficacy and safety of treatment with tislelizumab as part of an individualized strategy. The study is open-label, meaning that both the medical staff and the patient know which medications are being administered. The treatment is adjusted based on the response seen on the PET scan. All patients receive two doses of 200 mg tislelizumab 21 days apart. A PET-CT scan is then performed: Patients with a negative PET scan (good response) receive four additional doses of tislelizumab. Patients with a positive PET scan (insufficient response) also receive four doses of tislelizumab, plus four cycles of chemotherapy with AVD (adriamycin [doxorubicin], vinblastine, dacarbazine). For study participants between the ages of 18 and 60, radiation therapy is administered afterward only if the PET imaging remains positive. All patients over the age of 60 receive radiation therapy afterward regardless of the PET scan results. Treatment as part of the study lasts for up to 12 months, during which the efficacy of the therapy and the occurrence of side effects from the various medications are evaluated. The key factor is whether or when the disease progresses while on therapy. The primary endpoint of the study is progression-free survival after one year.

Women and men aged 18 and older with newly diagnosed, early-stage, high-risk cHL are eligible to participate in this study.