Project description:In recent years, the treatment paradigm for patients with chronic lymphocytic leukemia (CLL) has moved away from chemoimmunotherapy (CIT) toward the use of novel targeted agents. Commercially available drugs, including Bruton's tyrosine kinase inhibitors and the BCL2 inhibitor venetoclax, often used in combination with anti-CD20 monoclonal antibodies, are now the mainstay of therapy both in the frontline and in relapsed settings. As the landscape for CLL management evolves, therapeutic endpoints need to be redefined. Detection of measurable residual disease (MRD) is a sensitive tool to identify disease burden following treatment with several therapeutic regimens in CLL (including CIT, venetoclax-based regimens, and cellular therapies), and it has demonstrated prognostic value. Despite recent advances, the utility of MRD-directed therapy and attempts to eradicate it in routine clinical practice remain debated. There is little comparative data from clinical trials on the best assay to determine undetectable MRD (U-MRD) and whether its monitoring can lead to changes in treatment strategies. Our review discusses the definitions of MRD, assays for its detection, and its impact on long-term survival outcomes for patients with a CLL diagnosis.
Project description:Stereotactic body radiation therapy (SBRT) has an evolving role in the management of hepatocellular carcinoma (HCC), largely due to recent advances in imaging technology. Often utilized in situations where other locoregional therapies are not feasible, SBRT has been demonstrated to be an effective treatment that confers high rates of durable local control. However, there is limited evidence to firmly establish its place in the treatment paradigm for HCC. In this article, we review the current evidence and highlight specific considerations in the multiple settings where SBRT may be used, including for primary HCC treatment and bridging/downstaging, as well as exploring the potential for SBRT in the treatment of extrahepatic oligo-metastatic HCC.
Project description:Mesothelin is a tumor antigen that is highly expressed in many human cancers, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. It is an attractive target for cancer immunotherapy because its normal expression is limited to mesothelial cells, which are dispensable. Several antibody-based therapeutic agents as well as vaccine and T-cell therapies directed at mesothelin are undergoing clinical evaluation. These include antimesothelin immunotoxins (SS1P, RG7787/LMB-100), chimeric antimesothelin antibody (amatuximab), mesothelin-directed antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), live attenuated Listeria monocytogenes-expressing mesothelin (CRS-207, JNJ-64041757), and chimeric antigen receptor T-cell therapies. Two antimesothelin agents are currently in multicenter clinical registration trials for malignant mesothelioma: amatuximab in the first-line setting and anetumab ravtansine as second-line therapy. Phase II randomized clinical trials of CRS-207 as a boosting agent and in combination with immune checkpoint inhibition for pancreatic cancer are nearing completion. These ongoing studies will define the utility of mesothelin immunotherapy for treating cancer.
Project description:Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into the cellular and molecular mechanisms underlying these variable responses will bring us closer to developing more effective therapeutics. To assess these mechanisms, non-invasive imaging techniques provide valuable whole-body information with precise targeting. An example of such is immuno-PET (Positron Emission Tomography), which employs radiolabeled antibodies to detect specific molecules of interest. Nanobodies, as the smallest derived antibody fragments, boast ideal characteristics for this purpose and have thus been used extensively in preclinical models and, more recently, in clinical early-stage studies as well. Their merit stems from their high affinity and specificity towards a target, among other factors. Furthermore, their small size (~14 kDa) allows them to easily disperse through the bloodstream and reach tissues in a reliable and uniform manner. In this review, we will discuss the powerful imaging potential of nanobodies, primarily through the lens of imaging malignant tumors but also touching upon their capability to image a broader variety of nonmalignant diseases.
Project description:The current standard of care for smoldering multiple myeloma (SMM) is observation until there is end-organ involvement. With newer and more effective treatments available, a question that is increasingly asked is whether early intervention in patients with SMM will alter the natural history of their disease. Herein, we review the evolving definition of SMM and risk stratification models. We discuss evidence supporting early intervention for SMM-both as a preventative strategy to delay progression and as an intensive treatment strategy with a goal of potential cure. We highlight ongoing trials and focus on better defining who may require early intervention.