Intravenous immunoglobulins (IVIG) in severe/critical COVID-19 adult patients.

The coronavirus disease 2019 (COVID-19) pandemic has become a huge obstacle to the health system due to the high rate of contagion. It is postulated that intravenous immunoglobulins (IVIG) can lower the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related inflammation and prevent the development of acute respiratory distress syndrome (ARDS). The main advantages of IVIG treatment might be targeting cytokine storm in severe and critical COVID-19 by influences on complement, innate immune cells, effector T-cells, and Tregs. Randomized clinical trials (RCTs) and non-RCTs evaluating the safety and efficacy of IVIG in patients with severe/critical COVID-19 were performed. It seems that early administration of high-dose IVIG (in the acceleration phase of the disease) in severe or especially critical COVID-19 may be an effective therapeutic option, but there are no strong data to use it routinely. The results regarding mortality reduction are inconclusive. Additionally, IVIG treatment carries a risk of complications that should be considered when initiating treatment. However, given the COVID-19 mortality rate and limited therapeutic options, the use of IVIG is worth considering. This review summarizes the development and highlights recent advances in treatment with IVIG of severe/critically ill COVID-19 patients.

Sacituzumab Govitecan-hziy in Breast Cancer.

Trophoblast cell-surface antigen-2 (Trop-2) is a transmembrane calcium signal transducer and its overexpression is common in many types of malignant epithelial tumors, including breast cancer (BC). Sacituzumab govitecan-hziy (SG), the anti-Trop-2 antibody-drug conjugate, resulted in a significant survival benefit over chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). The greatest efficacy was observed in those who had a medium or high Trop-2 score. However, the importance of Trop-2 as a potential predictive factor requires further research. Elderly patients also appear to benefit from treating with SG. While the early results are encouraging, the ultimate benefit of SG in patients with brain metastases has yet to be determined. Early phase studies have shown that SG is also active in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic BC. The most common side effects of SG are nausea, neutropenia and diarrhea. Currently, several clinical trials are in progress with SG in monotherapy and in combination treatment for various types of BC. Taken together, SG should be considered as a new standard of care in patients with pretreated mTNBC. This review summarizes the development and highlights recent advances of the SG in BC.

Serum free light chains in solid organ transplant recipients.

Immunoglobulin is built by a pair of identical heavy and a pair of identical light chains. Light chains are produced in excess compared to heavy chains. Free light chains (FLCs) are those which are not combined with heavy chains. Currently, numerous assays are available for the measurement of serum FLCs (sFLCs). These assays cannot be used interchangeably, and renal function should be taken into account in interpreting test results. Levels of kappa and lambda sFLCs are usually used to diagnose and monitor plasma cell dyscrasias. However, the clinical relevance of sFLCs is being investigated in patients with a variety of diseases, including patients after transplantation. There are contradictory results regarding the usefulness of sFLCs in the prediction of post-transplant lymphoproliferative disorder (PTLD). However, it seems that sFLCs may be helpful in the prediction of early-onset PTLD. Some studies have shown that low levels of sFLCs are associated with a higher risk of infection in patients after transplantation. This review summarizes and highlights recent advances in the utility of sFLCs in the prediction of PTLD and infection, and inflammation assessment in patients after solid organ transplantation. Moreover, the influence of immunosuppressive treatment on sFLCs levels is described briefly.

Pembrolizumab and atezolizumab in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is defined by a lack of expression of both estrogen (ER) and progesterone (PgR) receptors as well as human epidermal growth factor receptor 2 (HER2) and is associated with poor prognosis. Moreover, the systemic treatment options are limited. However, the TNBC is more likely than other breast cancer subtypes to benefit from immune checkpoint blockade therapy due to its higher immunogenicity, higher enrichment by tumour-infiltrating lymphocytes (TILs), and higher levels of programmed cell death ligand 1 (PD-L1) expression. Thus far, atezolizumab was approved in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic TNBC whose tumours express PD-L1. Currently, it seems that PD-L1-positive subgroup will potentially benefit the most from the immune checkpoint inhibitor (ICI) treatment. Moreover, it seems that better results are seen when an ICI is given as first-line treatment than when an ICI is given in later lines of treatment for advanced TNBC/metastatic TNBC. Recently, pembrolizumab has demonstrated promising results in early-stage TNBC what can lead in near future to its approval in (neo)adjuvant setting. This review summarizes the development and highlights recent advances of the atezolizumab and pembrolizumab in early and advanced/metastatic TNBC.

Oligometastatic breast cancer.

Metastatic breast cancer (MBC) is considered as incurable. The group of patients with oligometastatic disease (a few metastatic lesions and organs involved) apparently have better prognosis. It is claimed that, these patients could be treated with curative intent, and multidisciplinary aggressive approach should be considered. Despite the lack of strong data it is increasingly accepted in clinical practice. Currently, the appropriate candidate would be young woman with good performance status, low tumour burden with long disease-free interval. Because for them with already favorable nature of their disease, aggressive treatment has greater chances to improve survivals. Local ablative treatment (radiotherapy/surgery) has a crucial role in this setting. Available mainly from retrospective in nature long-term results are encouraging but need confirmation in prospective randomized studies. In this review, I discuss the definition of oligometastatic disease, its nature, currently available data and ongoing prospective randomized trials dedicated to oligometastatic breast cancer patients.

Cyclin-dependent kinase 4/6 inhibitors in hormone receptor-positive early breast cancer: preliminary results and ongoing studies.

The cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitors (CDK4/6i) induce cell cycle arrest in the G1 phase what eventually can prevent the proliferation of cancer cells. The CDK4/6i have changed the landscape of treatment options for ER-positive, HER2-negative metastatic breast cancer. Currently, palbociclib, ribociclib, and abemaciclib are approved by the US Food and Drug Administration in this setting. This success encouraged the researchers to examine CDK4/6i activity in (neo)adjuvant setting. In this review, clinical data to date and ongoing clinical trials with palbociclib, ribociclib, and abemaciclib in the early breast cancer are discussed. A literature search of these topics was carried out using PubMed and data reported at international oncology meetings and clinicaltrials.gov were included. Currently, we have the early promising data from Phase II clinical trials of CDK4/6i efficacy in the neoadjuvant setting in women with HR-positive breast cancer. Moreover, there are numerous studies that are in progress today in (neo)adjuvant setting.

Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib.

PURPOSE: The cyclin D-cyclin dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway plays a crucial role in cell cycle progression and its dysregulation is an important contributor to endocrine therapy resistance. CDK4/6 inhibitors trigger cell cycle arrest in Rb protein (pRb)-competent cells. Recent years have seen the development of selective CDK4/6 inhibitors, which have delivered promising results of efficacy and manageable safety profiles. The main objective of this review is to discuss preclinical and clinical data to date, and ongoing clinical trials with palbociclib, ribociclib, and abemaciclib in breast cancer. METHODS: A literature search of above topics was carried out using PubMed and data reported at international oncology meetings and clinicaltrials.gov were included. RESULTS: The highly selective oral CDK4/6 inhibitors have been tested in combination with endocrine therapy in Phase III studies in metastatic breast cancer. Results led to the US Food and Drug Administration approval of palbociclib (PD0332991) and ribociclib (LEE011), and abemaciclib (LY2835219) is in development. Studies of these agents, in combination with endocrine therapy, are also underway in ER-positive early breast cancer in the neoadjuvant and adjuvant settings. Moreover, they are also being investigated with other agents in the advanced setting and in triple negative breast cancer. CONCLUSIONS: After having demonstrated impressive activity in ER-positive, HER2-negative metastatic breast cancer, currently CDK4/6 inhibitors are in further development. It is obvious that this class of agents with their efficacy, low and easily manageable toxicity, and oral dosage is a very important treatment option for breast cancer patients.

The first liquid biopsy test approved. Is it a new era of mutation testing for non-small cell lung cancer?

Specific mutations in epidermal growth factor receptor (EGFR) gene are predictive for response to the EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer patients (NSCLC). According to international guidelines, the molecular testing in patients with advanced NSCLC of a non-squamous subtype is recommended. However, obtain a tissue sample could be challenging. Liquid biopsy allows to determine patients suitable for EGFR-targeted therapy by analysis of circulating-free tumor DNA (cfDNA) in peripheral blood samples and might replace tissue biopsy. It allows to acquire a material in convenient minimally invasive manner, is easily repeatable, could be used for molecular identification and molecular changes monitoring. Many studies show a high concordance rate between tissue and plasma samples testing. When U.S. Food and Drug Administration (FDA) approved the first liquid biopsy test, analysis of driver gene mutation from cfDNA becomes a reality in clinical practice for patients with NSCLC.