ROLE OF CHECKPOINT INHIBITION IN GERMANY

Abstract

Immune checkpoint inhibition (ICI) has demonstrated an overall excellent benefit-to-risk profile in the treatment of classical Hodgkin lymphoma (cHL); however, cure remains an exception to the rule. The German Hodgkin Study Group (GHSG) has identified several areas of unmet need for ICI development in cHL. First, we aim to better understand the role of immune checkpoints in the interplay between Hodgkin/Reed-Sternberg malignant cells and the abundant microenvironment. Second, we aim to improve efficacy of ICI in multiple relapsed/refractory (r/r) cHL patients, as complete response rates are infrequent and median PFS is still quite limited. Therefore, combination therapies with alternative ICIs targeting TIGIT, LAG3, or TIM3, or combinations with conventional cytotoxic drugs need to be investigated. The GHSG has focused on evaluating the abscopal effects of radiotherapy to improve ICI in multiple r/r cHL. Third, the GHSG strongly believes that ICI should be able to improve first-line therapy of cHL. The GHSG is currently conducting clinical trials to de-escalate the chemotherapy intensity. In early favourable stage cHL patients, we hypothesize that ICI can replace chemotherapy in the combined modality therapy approach. In early unfavourable stage cHL, we use our PET-adapted design to select well-responding patients and remove chemotherapy and/or radiotherapy from the treatment strategy. In advanced stage cHL, we aim to reduce cumulative exposure to conventional chemotherapy. We hypothesize that the combination of anti-PD-1 antibody therapy with our intensive chemotherapy should act synergistically and more patients should achieve an early metabolic complete response. These patients could then be treated with only 4 cycles of combined PD1 chemotherapy. Overall, this new treatment principle should serve to overcome chemotherapy resistance and improve the efficacy of established therapeutic regimens, while reducing the treatment burden for our cHL patients. Keywords: Hodgkin lymphoma, immunotherapy No conflicts of interests pertinent to the abstract.