Abstract
The programmed-death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) pathways are inhibitory immune checkpoints involved in the escape of cancer cells from the immune system. Inhibition of these immune checkpoints can lead to the induction of body’s immune response to these cancer cells. To activate the immune system against the tumor cells, various monoclonal antibodies targeting these pathways have been developed. Many of such antibodies have been approved for therapy in solid tumor malignancies and now some hematological malignancies. Here, we review the available data regarding the response to PD-1 and CTLA-4 pathway blockade in hematological malignancies including Hodgin lymphoma, non-Hodgkin lymhoma, multiple myeloma and myeloid neoplasms as well as before and after hematopoietic cell transplantation. We also discuss the specific concerns and differences related to their use in hematological malignancies (HMs) as compared to solid tumors.
Highlights
Cancer therapy has been revolutionized by the discovery of the interplay between cancer cells and the host immune system
We review the available data on immune checkpoint inhibition in hematological malignancies
We review the differences in the expression of checkpoints in different pathologies and their impact on therapy outcomes
Summary
Cancer therapy has been revolutionized by the discovery of the interplay between cancer cells and the host immune system. In 2008, Berger et al, reported outcomes of phase I clinical trial of humanized IgG1 monoclonal antibody, pidilizumab, enrolling 17 patients with HMs, including 4 patients with NHL (two patients with DLBCL, one follicular lymphoma (FL), and one acute lymphocytic cell lymphoma) [19]. Multiple checkpoint inhibitors (CPI) have been examined as a part of combination therapies that reverse tumor-mediated immune suppression and expand myeloma-reactive T-cells It demonstrates great potential, the therapeutic efficacy of PD-1/PD-L1 blockade and immune-based strategies, in general, will likely depend on a complicated understanding of the immunologic milieu in a disease setting. Around the end of 2017, FDA had placed multiple studies on full or partial hold due to increased reports of patients’ deaths related to treatment toxicity
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