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Current Opinion in Oncology Nov 2023B-cell maturation antigen (BCMA)-directed T-cell immunotherapies, such as chimeric antigen receptor T-cells (CAR T-cells) and bispecific antibodies (BsAbs) have markedly...
PURPOSE OF REVIEW
B-cell maturation antigen (BCMA)-directed T-cell immunotherapies, such as chimeric antigen receptor T-cells (CAR T-cells) and bispecific antibodies (BsAbs) have markedly improved the survival of triple-class refractory multiple myeloma (MM). However, the majority of patients still develops disease progression, underlining the need for new agents for these patients.
RECENT FINDINGS
Novel T-cell redirecting BsAbs targeting alternative tumor-associated antigens have shown great promise in heavily pretreated MM, including patients previously exposed to BCMA-directed therapies. This includes the G-protein-coupled receptor class 5 member D (GPRC5D)-targeting BsAbs talquetamab and forimtamig, as well as the Fc receptor-homolog 5 (FcRH5)-targeting BsAb cevostamab. Toxicity associated with these BsAbs includes cytokine-release syndrome, cytopenias, and infections. In addition, GPRC5D-targeting BsAbs are associated with specific 'on target/off tumor' toxicities including rash, nail disorders, and dysgeusia. Trispecifc antibodies targeting two different MM-associated antigens to prevent antigen escape are in early clinical development, as well as trispecific antibodies (TsAbs) that provide an additional co-stimulatory signal to T-cells to prevent their exhaustion.
SUMMARY
Various T-cell redirecting BsAbs are in advanced stages of clinical development with promising activity and a manageable toxicity profile. Ongoing studies are evaluating combination strategies, fixed-duration treatment, and use of BsAbs in earlier lines of therapy. TsAbs hold great promise for the future.
PubMed: 37501530
DOI: 10.1097/CCO.0000000000000983 -
Journal of Clinical Oncology : Official... Oct 2023JCO Patients with Kirsten rat sarcoma viral oncogene homolog ()-mutated non-small-cell lung cancer (NSCLC) and untreated CNS metastases have a worse prognosis than...
JCO Patients with Kirsten rat sarcoma viral oncogene homolog ()-mutated non-small-cell lung cancer (NSCLC) and untreated CNS metastases have a worse prognosis than similar patients without mutations. Adagrasib has previously demonstrated CNS penetration preclinically and cerebral spinal fluid penetration clinically. We evaluated adagrasib in patients with -mutated NSCLC and untreated CNS metastases from the KRYSTAL-1 trial (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), in which adagrasib 600 mg was administered orally, twice daily. Study outcomes included the safety and clinical activity (intracranial [IC] and systemic) by blinded independent central review. Twenty-five patients with -mutated NSCLC and untreated CNS metastases were enrolled and evaluated (median follow-up, 13.7 months); 19 patients were radiographically evaluable for IC activity. Safety was consistent with previous reports of adagrasib, with grade 3 treatment-related adverse events (TRAEs) in 10 patients (40%) and one grade 4 (4%) and no grade 5 TRAEs. The most common CNS-specific TRAEs included dysgeusia (24%) and dizziness (20%). Adagrasib demonstrated an IC objective response rate of 42%, disease control rate of 90%, progression-free survival of 5.4 months, and median overall survival of 11.4 months. Adagrasib is the first KRAS inhibitor to prospectively demonstrate IC activity in patients with -mutated NSCLC and untreated CNS metastases, supporting further investigation in this population.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Proto-Oncogene Proteins p21(ras); Lung Neoplasms; Acetonitriles; Central Nervous System Neoplasms; Mutation; Neoplasms, Second Primary
PubMed: 37327468
DOI: 10.1200/JCO.23.00046 -
Cancers Sep 2023Post-oropharyngeal cancer treatment complications include a multitude of oral side effects that impact overall survival and quality of life. These include acute and... (Review)
Review
Post-oropharyngeal cancer treatment complications include a multitude of oral side effects that impact overall survival and quality of life. These include acute and chronic conditions affecting the oral cavity and head and neck, such as mucositis, infection, xerostomia, dysgeusia, radiation caries, osteonecrosis, and trismus. This review will summarize the most common oral complications from oropharyngeal cancer therapy. The authors would like to point out that the literature cited frequently combines oropharyngeal and head and neck cancer results. If recommendations are made strictly related to oropharyngeal cancers, this will be highlighted.
PubMed: 37760517
DOI: 10.3390/cancers15184548 -
Nutrients Dec 2023Throughout their experience of illness and during the course of treatment, a substantial proportion of cancer patients are prone to develop nutritional and/or metabolic... (Review)
Review
Throughout their experience of illness and during the course of treatment, a substantial proportion of cancer patients are prone to develop nutritional and/or metabolic disturbances. Additionally, cancer patients often encounter long-term side effects from therapies, which may lead to impaired digestion, nutrient absorption or bowel motility. Therefore, the preservation and maintenance of an optimal and balanced nutritional status are pivotal to achieving a better prognosis, increasing the tolerance and adherence to cancer therapies and improving the overall quality of life. In this context, personalized nutritional programs are essential for addressing conditions predisposing to weight loss, feeding difficulties, digestion problems and intestinal irregularity, with the goal of promoting adequate nutrient absorption and minimizing the detrimental effects of treatment regimens. The focus of this research is to examine the most common clinical conditions and metabolic changes that cancer patients may experience, including stomatitis, xerostomia, diarrhea, nausea, vomiting, dysphagia, sub-occlusion, dysgeusia, dysosmia, anorexia, and cachexia. Furthermore, we present a pragmatic example of a multidisciplinary workflow that incorporates customized recipes tailored to individual clinical scenarios, all while maintaining the hedonic value of the meals.
Topics: Humans; Quality of Life; Nutritional Status; Neoplasms; Cachexia; Weight Loss
PubMed: 38140327
DOI: 10.3390/nu15245068 -
The Lancet. Microbe Aug 2023The most prevalent symptoms of post-COVID-19 condition are pulmonary dysfunction, fatigue and muscle weakness, anxiety, anosmia, dysgeusia, headaches, difficulty in... (Review)
Review
The most prevalent symptoms of post-COVID-19 condition are pulmonary dysfunction, fatigue and muscle weakness, anxiety, anosmia, dysgeusia, headaches, difficulty in concentrating, sexual dysfunction, and digestive disturbances. Hence, neurological dysfunction and autonomic impairments predominate in post-COVID-19 condition. Tachykinins including the most studied substance P are neuropeptides expressed throughout the nervous and immune systems, and contribute to many physiopathological processes in the nervous, immune, gastrointestinal, respiratory, urogenital, and dermal systems and participate in inflammation, nociception, and cell proliferation. Substance P is a key molecule in neuroimmune crosstalk; immune cells near the peripheral nerve endings can send signals to the brain with cytokines, which highlights the important role of tachykinins in neuroimmune communication. We reviewed the evidence that relates the symptoms of post-COVID-19 condition to the functions of tachykinins and propose a putative pathogenic mechanism. The antagonism of tachykinins receptors can be a potential treatment target.
Topics: Humans; Substance P; COVID-19; Tachykinins; Neuropeptides; Receptors, Tachykinin
PubMed: 37327802
DOI: 10.1016/S2666-5247(23)00111-8 -
Journal of Renal Nutrition : the... May 2024Dysgeusia is a common altered taste perception in chronic kidney disease patients. The study aims to identify available treatments for educating, screening, and... (Review)
Review
Dysgeusia is a common altered taste perception in chronic kidney disease patients. The study aims to identify available treatments for educating, screening, and clinically managing dysgeusia in this population. A scoping review was conducted following the protocol of Arksey and O'Malley, incorporating the Joanna Briggs Institute methodology, and adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Among the 424 identified records, 13 studies were included. Screening methodologies, educational strategies, particularly a hospital-based program focusing on salt reduction, showed a significant improvement in dysgeusia (P < .001). The identified clinical treatments exclusively included oral zinc supplementation, with dosages ranging from 50 to 220 mg, reporting heterogeneous results not consistent across different studies. The personalized management of dysgeusia associated with chronic kidney disease is crucial, requiring targeted education and treatment protocols to prevent and address nutritional complications such as malnutrition.
PubMed: 38729584
DOI: 10.1053/j.jrn.2024.04.005