Nejvíce citovaný článek - PubMed ID 26806146
Immunomodulatory drugs in AL amyloidosis
- MeSH
- amyloidóza * diagnóza genetika MeSH
- lehké řetězce imunoglobulinů genetika MeSH
- lidé MeSH
- molekulární patologie MeSH
- mutace MeSH
- plazmatické buňky MeSH
- primární amyloidóza * diagnóza genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- Názvy látek
- lehké řetězce imunoglobulinů 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.
- Klíčová slova
- PD-1, PD-L1, durvalumab, multiple myeloma, nivolumab, pembrolizumab, safety, toxicity,
- MeSH
- antigeny CD279 antagonisté a inhibitory MeSH
- cílená molekulární terapie MeSH
- imunomodulace účinky léků MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- mnohočetný myelom farmakoterapie imunologie metabolismus patologie MeSH
- preklinické hodnocení léčiv MeSH
- protinádorové látky imunologicky aktivní farmakologie terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- signální transdukce účinky léků MeSH
- T-lymfocyty účinky léků imunologie metabolismus MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antigeny CD279 MeSH
- PDCD1 protein, human MeSH Prohlížeč
- protinádorové látky imunologicky aktivní 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
- lidé MeSH
- paraproteinemie diagnostické zobrazování patologie MeSH
- průtoková cytometrie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH