EHA Library - The official digital education library of European Hematology Association (EHA)

Immune checkpoint inhibitors
EHA Library. Younes A. 06/14/17; 185023 Topic: 3A B-cell neoplasms and B-cell disorders
Dr. Anas Younes
Dr. Anas Younes
Contributions
Learning Objectives
Andreas Engert - Chair Introduction

Immunotherapy of malignant lymphoma has fascinated both, basic scientists and clinical researchers for decades. This was particularly true for those lymphomas that were mainly composed of reactive cells such as Hodgkin lymphoma and some of the low grade lymphomas. With the advent of more sophisticated techniques such as single cell analysis and gene expression profiling, our understanding of the microenvironment playing an important role in the pathogenesis of different malignant lymphoma has clearly improved. Particularly, the different immune-checkpoint-pathways have substantially contributed to our better understanding of the interaction of the immune system and the malignant cells. Here, therapeutic targeting of the PD-1 checkpoint resulted in high response rates in malignant lymphoma in a basket phase-IB trial. Particularly classical Hodgkin lymphoma (cHL) patients responded with an overall response rate of 66% in the initial phase I when treated with Nivolumab. Responses were also seen with another anti-PD-1 monoclonal antibody, Pembrolizumab. Both drugs resulted in similar outcomes in cHL patients failing several lines of treatment. The follow-up phase-II trials led to the registration of Nivolumab in the US and Europe; the registration of Pembolizumab is expected in 2017. A number of clinical trials currently evaluate these drugs either alone or in combination in different malignant lymphoma. Clinical trials are also ongoing in which checkpoint inhibitors are being combined with truncated chemotherapy.

The combination of immune-checkpoint-inhibition and allogeneic transplant has resulted in some severe side effects such as severe acute GVHD when allo-TX was performed after prior immune-checkpoint-inhibition. Particularly, progressive lymphoma patients treated with allo-TX followed by PD-1 inhibitors showed severe acute GVHD but there appears to be a learning curve. On the other hand, immune-checkpoint-inhibition in malignant lymphoma might lead to less lymphoma patients receiving an allo-transplant.

Learning Objectives of the manuscript
After viewing this presentation the participant will be able to:
- Understanding the role of the microenvironment in B-cell lymphoma.
- Current status of PD-1 inhibition in lymphoma.
- Update on auto- and allo-transplant in lymphoma.

Learning Objectives of the presentation
After viewing this presentation the participant will be able to:

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