A checkpoint inhibitor (pembrolizumab) as an additional medication in the treatment of relapsed or uncontrollable 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 and is generally very treatable. The exact causes are unclear, but genetic factors and infections such as the Epstein-Barr virus may play a role. Treatment depends on the stage and risk classification of the disease. However, if the disease cannot be brought under control despite standard treatment (refractory) or if it becomes active again over time (recurrence), the prognosis worsens despite the medications then used. The therapies used in such cases often have relatively severe side effects, so an improvement in treatment options for this situation would be desirable. Typically, combinations of drugs are used in this situation, such as those based on the so-called “ICE” regimen (ifosfamide, carboplatin, etoposide) or the “DHAP” (dexamethasone, high-dose cytarabine, cisplatin) regimen. One mechanism of action already used in cHL involves checkpoint inhibitors, which specifically interfere with signaling pathways between cancer cells, thereby causing their death. These have already been used with great success in other types of cancer.

The goal of the Pembro-CORE study (Phase 2 study) is to further investigate the efficacy and safety of the combination therapy consisting of the drug pembrolizumab (checkpoint inhibitor) and standard chemotherapy (ICE or DHAP) in a selected group of patients. All medications are already approved for the treatment of cHL. As part of the study, all patients receive the same treatment, and the study is open-label, meaning that both the medical staff and the patient know which medications are being administered. Initially, patients will receive a single dose of 200 mg of pembrolizumab via an intravenous line. This will be followed by two cycles of the combination therapy with pembrolizumab + ICE. Afterward, a PET-CT scan will be performed to assess the response to therapy. If the imaging shows no further signs of malignant tissue changes, two additional cycles of pembrolizumab plus ICE are administered. If malignant tissue changes are still present, 2–4 cycles of pembrolizumab plus DHAP are administered. After completion of this initial treatment, the next phase of therapy begins. During this phase, an additional 6 cycles of pembrolizumab are administered. If no response to treatment is observed after 4 cycles of combination chemotherapy, high-dose chemotherapy or another standard treatment should be considered as an alternative. As part of the treatment, the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factor is whether or when the disease progresses again during therapy. The primary endpoint of the study is a complete metabolic response to treatment (as seen on PET-CT imaging) 3 months after completion of the combination therapy.

Women and men between the ages of 18 and 65 with cHL are eligible to participate in this study. The disease must either be refractory or have recurred for the first time following initial therapy (first relapse).