PD‐1/PD‐L1 inhibitors in haematological malignancies: update 2017

Abstract

The introduction of PD-1/PD-L1 pathway inhibitors is an important landmark in solid oncology with unprecedented practice-changing activity in various types of solid tumours. Among haematological malignancies, PD-1/PD-L1 inhibitors have been successful, so far, only in the treatment of classical Hodgkin lymphoma, which typically exhibits an over-expression of PD-1 ligands (PD-L1, PD-L2) due to alterations in chromosome 9p24.1. Such positive outcomes led to the US Food and Drug Administration approval of nivolumab use in relapsed Hodgkin lymphoma in 2016 as the first haematological indication. Although the results in other lymphoid malignancies have not been so striking, blockade of the PD-1/PD-L1 axis has led to meaningful responses in other lymphoma types such as diffuse large B-cell lymphoma, follicular lymphoma or several T-cell lymphomas. Monotherapy with PD-1/PD-L1 inhibitors in chronic lymphocytic leukaemia and multiple myeloma has been unsatisfactory, suggesting that a combinational approach with other synergistic drugs is needed. In the case of multiple myeloma, immunomodulatory agents together with corticosteroids represent the most promising combinations. Among myeloid malignancies, the anti-PD-1 monoclonal antibodies are examined dominantly in acute myeloid leukaemia and myelodysplastic syndromes in combination with potentially synergistic hypomethylating drugs such as 5-azacitidine, resulting in promising outcomes that warrant further investigation. We have described all available clinical results of PD-1/PD-L1 inhibitors in haematological malignancies and discussed related toxicities, as well as highlighted crucial preclinical studies in this review.

Targeting immune checkpoints in breast cancer: an update of early results

“…ICB uses mAbs targeting inhibitory immune checkpoints and has demonstrated impressive results in a variety of solid tumours and haematologic malignancies. [9][10][11][12][13][14][15][16][17][18] Accordingly, some of these ICB drugs have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of melanoma, non-small cell lung cancer (NSCLC), urothelial carcinoma, renal cell carcinoma, head and neck cancer and classical Hodgkin lymphoma.…”

Second cancers in Hodgkin's lymphoma long-term survivals: A 60-year single institutional experience with real-life cohort of 871 patients

“…Pretreatment neutrophil/lymphocyte ratio and platelet/lymphocyte ratio was shown to be prognostic of progression in early stage HL . Current renaissance in immunotherapy will subsequently influence the treatment results and possibly the risk of SC, similarly as in novel treatment approaches in solid cancers …”

“…As a consequence, excess mortality ˃15 years after successful treatment of HL may be due to adverse side effects rather than HL itself, especially in patients with clinical stages I and II . Appropriate surveillance guidelines for HL survivors are needed to reduce mortality of this iatrogenic SC, especially with continuing efforts and achievements in the upfront treatment of HL patients including advances in immunotherapy …”

Induction of Neoantigen-Specific Cytotoxic T Cells and Construction of T-cell Receptor–Engineered T Cells for Ovarian Cancer

“…Immune checkpoint inhibitors (anti-programmed cell death 1 (PD-1) antibodies and anti-programmed cell death ligand 1 (PD-L1) inhibitors) have achieved great success for several cancer types (6)(7)(8)(9). Accumulating evidences from patients who responded well to immune checkpoint inhibitors imply that tumor regression is achieved by activation of cytotoxic T cells targeting neoantigens, which are generated mostly by non-synonymous mutations in cancer cells (10)(11)(12).…”