Background: Despite high efficacy of first-line therapies for classical Hodgkin lymphoma (cHL), treatment for patients with relapse has been only moderately successful. The current standard of care (SOC) in most cases includes salvage chemotherapy followed by high-dose chemotherapy (HD-CT) and autologous stem cell transplant. This approach only achieves long-term remission in about half of patients without proven significant benefit in overall survival. Moreover, patients suffer from high treatment associated toxicity and severe short- and long-term side effects. Recent studies emphasize the potential of immunotherapy-based approaches in treating cHL, with PD-1 based salvage regimens like P-GVD, P-ICE and N-ICE achieving response rates of up to 95%.
Objective: The Pembro-CORE trial is investigating a HD-CT-free treatment for patients with first relapse of cHL by combining Pembrolizumab with salvage chemotherapy. This multicentric phase II study, initiated in March 2024, has thus far recruited three patients. According to protocol, patients receive one cycle of Pembrolizumab and two cycles of P-ICE (Pembrolizumab, Ifosfamide, Carboplatin, Etoposide). After PET restaging, responders receive two cycles of P-ICE. Non-responders switch to two cycles of P-DHAP (Pembrolizumab, Dexamethasone, High-Dose Cytarabine, Cisplatin). A second PET restaging after five cycles determines further treatment; PET-positive cases are treated outside the study according to SOC. Non-responders in the P-ICE arm may receive two additional cycles of P-DHAP followed by a third restaging. If they remain PET-positive, they will also be treated according to SOC. Treatment concludes with consolidating Pembrolizumab until final staging. Complete metabolic response rate, defined as the proportion of patients with a Deauville score of 1-3 in restaging after treatment with 1x Pembrolizumab + 4 cycles of Pembrolizumab and chemotherapy (4x P-ICE or 2x P-ICE + 2x P-DHAP) is the primary endpoint. This is the proportion of patients that can be spared from HD-CT. Secondary endpoints include PFS, OS and patient reported outcomes. The trial is complemented by a scientific side program.
Outlook: The Pembro-CORE trial investigates a novel approach to treatment of first relapsed or refractory classical Hodgkin's lymphoma by combining Pembrolizumab with PET-guided salvage chemotherapy. If succesful, the trial might contribute to the omission of HD-CT in patients with relapsed HL.
Hishan Tharmaseelan, Sarah Gillessen, Ina Bühnen, Helen Kaul, Carsten Kobe, Wolfram Klapper, Michael Fuchs, Sven Borchmann, Paul J. Bröckelmann, Peter Borchmann, Bastian von Tresckow