• MeSH
• Clone Cells drug effects   pathology   MeSH
• Humans MeSH
• Survival Rate MeSH
• Multiple Myeloma drug therapy   pathology   MeSH
• Antibodies, Monoclonal therapeutic use   MeSH
• Follow-Up Studies MeSH
• Plasma Cells drug effects   pathology   MeSH
• Prognosis MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• daratumumab MeSH Browser
• Antibodies, Monoclonal MeSH
• Antineoplastic Agents MeSH

Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK cell function occurring in MM.

• Keywords
• NK cells, activating receptors, immunotherapy, inhibitory receptors, microenvironment, multiple myeloma, niche,
• MeSH
• Biomarkers MeSH
• Killer Cells, Natural immunology   metabolism   MeSH
• Molecular Targeted Therapy MeSH
• Cytotoxicity, Immunologic MeSH
• Immunity MeSH
• Immunomodulation drug effects   MeSH
• Humans MeSH
• Disease Management MeSH
• Multiple Myeloma diagnosis   etiology   metabolism   therapy   MeSH
• Disease Susceptibility MeSH
• Tumor Microenvironment drug effects   immunology   MeSH
• Prognosis MeSH
• Receptors, Natural Killer Cell genetics   metabolism   MeSH
• T-Lymphocyte Subsets immunology   metabolism   MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Biomarkers MeSH
• Receptors, Natural Killer Cell MeSH

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

• MeSH
• Allergy and Immunology standards   MeSH
• Phenotype MeSH
• Consensus MeSH
• Humans MeSH
• Flow Cytometry methods   standards   MeSH
• Cell Separation methods   standards   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The treatment of cancer, especially of various types of solid tumors, has been revolutionized by the blockade of the PD-1/PD-L1 pathway by immune checkpoint inhibitors. Their success amongst hematologic malignancies, however, has been limited so far to the treatment of classic Hodgkin's lymphoma, which portrays a typical overexpression of PD-1 ligands (PD-L1, PD-L2) as a consequence of changes in chromosome 9p24.1. Their current application in multiple myeloma (MM) is rather uncertain, as discordant results have been reported by distinct research groups concerning especially the expression of PD-1/PD-L1 molecules on malignant plasma cells or on the responsible immune effector cell populations, respectively. In MM it seems that an approach based on combination treatment might be appropriate as unsatisfactory results have been yielded by monotherapy with PD-1/PD-L1 inhibitors. Immunomodulatory drugs, which are the current cornerstone of MM treatment, are the most logical partners as they possess many possibly synergistic effects. Nevertheless, the initially optimistic results have become disappointing due to the excessive and unpredictable toxicity of the combination of pembrolizumab with lenalidomide or pomalidomide. The FDA has suspended or put on hold several phase 3 trials in relapsed as well as in newly diagnosed myeloma patients. There are also other potentially synergistic and promising combinations, such as the anti-CD38 monoclonal antibody daratumumab, irradiation, etc. Not only the effective partner but also the correct timing of the initiation of the PD-1/PD-L1 inhibitors treatment seems to be of utmost importance. These strategies are currently being examined in various stages of myeloma such as during consolidation post autologous stem cell transplantation, targeting minimal residual disease or even in high risk smoldering myeloma.

• Keywords
• PD-1, PD-L1, durvalumab, multiple myeloma, nivolumab, pembrolizumab, safety, toxicity,
• MeSH
• Programmed Cell Death 1 Receptor antagonists & inhibitors   MeSH
• Molecular Targeted Therapy MeSH
• Immunomodulation drug effects   MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Multiple Myeloma drug therapy   immunology   metabolism   pathology   MeSH
• Drug Evaluation, Preclinical MeSH
• Antineoplastic Agents, Immunological pharmacology   therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols adverse effects   therapeutic use   MeSH
• Signal Transduction drug effects   MeSH
• T-Lymphocytes drug effects   immunology   metabolism   MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Programmed Cell Death 1 Receptor MeSH
• PDCD1 protein, human MeSH Browser
• Antineoplastic Agents, Immunological MeSH

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.

• Keywords
• haematological malignancy, myeloma, nivolumab, pembrolizumab, programmed death 1 receptor,
• MeSH
• B7-H1 Antigen antagonists & inhibitors   immunology   metabolism   MeSH
• Programmed Cell Death 1 Receptor antagonists & inhibitors   immunology   metabolism   MeSH
• Molecular Targeted Therapy MeSH
• Hematologic Neoplasms drug therapy   immunology   metabolism   pathology   MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Evidence-Based Medicine MeSH
• Antineoplastic Agents adverse effects   therapeutic use   MeSH
• Signal Transduction drug effects   MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• B7-H1 Antigen MeSH
• Programmed Cell Death 1 Receptor MeSH
• CD274 protein, human MeSH Browser
• PDCD1 protein, human MeSH Browser
• Antineoplastic Agents MeSH

Multiparameter flow cytometry (MFC) has become standard in the management of patients with plasma cell (PC) dyscrasias, and could be considered mandatory in specific areas of routine clinical practice. It plays a significant role during the differential diagnostic work-up because of its fast and conclusive readout of PC clonality, and simultaneously provides prognostic information in most monoclonal gammopathies. Recent advances in the treatment and outcomes of multiple myeloma led to the implementation of new response criteria, including minimal residual disease (MRD) status as one of the most relevant clinical endpoints with the potential to act as surrogate for survival. Recent technical progress led to the development of next-generation flow (NGF) cytometry that represents a validated, highly sensitive, cost-effective and widely available technique for standardized MRD evaluation, which also could be used for the detection of circulating tumor cells. Here we review current applications of MFC and NGF in most PC disorders including the less frequent solitary plasmocytoma, light-chain amyloidosis or Waldenström macroglobulinemia.

• MeSH
• Humans MeSH
• Paraproteinemias diagnostic imaging   pathology   MeSH
• Flow Cytometry methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

The introduction of PD-1/PD-L1 pathway inhibitors has marked a significant milestone in the treatment of various types of solid tumors. The current situation in multiple myeloma (MM) is rather unclear, as distinct research groups have reported discordant results. This discrepancy dominantly concerns the expression of PD-1/PD-L1 molecules as well as the identification of the responsible immune effector cell population. The results of monotherapy with PD-1/PD-L1 inhibitors have been unsatisfactory in MM, suggesting that a combination approach is needed. The most logical partners are immunomodulatory agents as they possess many synergistic effects. We are also proposing other rational and promising combinations (e.g., daratumumab, ibrutinib, anti-CD137) that warrant further investigation.

• Keywords
• Daratumumab, PD-1, PD-L1, durvalumab, ibrutinib, irradiation, multiple myeloma, nivolumab, pembrolizumab, pidilizumab,
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH