-
The New England Journal of Medicine Dec 2022G protein-coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells. Talquetamab, a bispecific antibody against...
BACKGROUND
G protein-coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells. Talquetamab, a bispecific antibody against CD3 and GPRC5D, redirects T cells to mediate killing of GPRC5D-expressing myeloma cells.
METHODS
In a phase 1 study, we evaluated talquetamab administered intravenously weekly or every other week (in doses from 0.5 to 180 μg per kilogram of body weight) or subcutaneously weekly, every other week, or monthly (5 to 1600 μg per kilogram) in patients who had heavily pretreated relapsed or refractory multiple myeloma that had progressed with established therapies (a median of six previous lines of therapy) or who could not receive these therapies without unacceptable side effects. The primary end points - the frequency and type of dose-limiting toxic effects (study part 1 only), adverse events, and laboratory abnormalities - were assessed in order to select the recommended doses for a phase 2 study.
RESULTS
At the data-cutoff date, 232 patients had received talquetamab (102 intravenously and 130 subcutaneously). At the two subcutaneous doses recommended for a phase 2 study (405 μg per kilogram weekly [30 patients] and 800 μg per kilogram every other week [44 patients]), common adverse events were cytokine release syndrome (in 77% and 80% of the patients, respectively), skin-related events (in 67% and 70%), and dysgeusia (in 63% and 57%); all but one cytokine release syndrome event were of grade 1 or 2. One dose-limiting toxic effect of grade 3 rash was reported in a patient who had received talquetamab at the 800-μg dose level. At median follow-ups of 11.7 months (in patients who had received talquetamab at the 405-μg dose level) and 4.2 months (in those who had received it at the 800-μg dose level), the percentages of patients with a response were 70% (95% confidence interval [CI], 51 to 85) and 64% (95% CI, 48 to 78), respectively. The median duration of response was 10.2 months and 7.8 months, respectively.
CONCLUSIONS
Cytokine release syndrome, skin-related events, and dysgeusia were common with talquetamab treatment but were primarily low-grade. Talquetamab induced a substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma. (Funded by Janssen Research and Development; MonumenTAL-1 ClinicalTrials.gov number, NCT03399799.).
Topics: Humans; Antibodies, Bispecific; Cytokine Release Syndrome; Dysgeusia; Multiple Myeloma; Neoplasm Recurrence, Local; Receptors, G-Protein-Coupled; T-Lymphocytes; CD3 Complex; Administration, Intravenous; Injections, Subcutaneous; Skin Diseases
PubMed: 36507686
DOI: 10.1056/NEJMoa2204591 -
Journal of Oral Biosciences Dec 2021Dysgeusia is a prevalent qualitative gustatory impairment that may affect food intake and quality of life. The facial (VII), glossopharyngeal (IX), and vagus (X) nerves... (Review)
Review
BACKGROUND
Dysgeusia is a prevalent qualitative gustatory impairment that may affect food intake and quality of life. The facial (VII), glossopharyngeal (IX), and vagus (X) nerves are the three cranial nerves responsible for sensing taste. Typically, dysgeusia is considered a general term for all taste disorders. In addition, dysgeusia may be a symptom of underlying systemic conditions such as diabetes mellitus, chronic kidney disease, respiratory infections, and nutritional deficiencies. Various subjective and objective diagnostic approaches are available to aid clinicians, each with its own set of benefits and drawbacks.
HIGHLIGHTS
Taste impairment can lead to a lack of enjoyment while eating, food aversion, and malnutrition, resulting in a decrease in the quality of life and loss of muscle mass. Therefore, the present review aims to address the probable etiologies, diagnostic aids, and management of dysgeusia. A broad search for studies was conducted using PubMed, Web of Science, Scopus, and Google Scholar. In addition, relevant studies found in the references of the selected articles were also studied.
CONCLUSION
Oral health care providers should be aware of the possible etiologies of dysgeusia, diagnostic tools, and treatment options. Accurate diagnosis of the cause of taste dysfunction has a significant impact on the management of taste impairment.
Topics: Awareness; Dysgeusia; Humans; Quality of Life; Taste; Taste Disorders
PubMed: 34487857
DOI: 10.1016/j.job.2021.08.006 -
Reviews in Medical Virology Jan 2022Initially, it was reported that coronavirus 2019 disease (Covid-19) affects respiratory, gastrointestinal and neurological systems, but the oral, olfactory and... (Review)
Review
Initially, it was reported that coronavirus 2019 disease (Covid-19) affects respiratory, gastrointestinal and neurological systems, but the oral, olfactory and integumentary systems are also involved. This review discusses various oral manifestations of Covid-19 reported in the literature along with possible underlying mechanisms. The reported manifestations include taste impairment, oral mucosal changes (petechiae, ulcers, plaque-like lesions, reactivation of herpes simplex virus 1(HSV1), geographical tongue and desquamative gingivitis) and dry mouth. The prominent location for mucosal lesions are tongue, palate and labial mucosa. The exact pathogenesis of these oral symptoms is not known. Angiotensin-converting enzyme 2 (ACE2) cell receptors are expressed in abundance on oral mucosa allowing severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) to infect them. Gustatory impairment along with olfactory changes is now listed as a symptom of Covid-19 by the World Health Organization, but further research is needed to confirm a link between reported additional oral symptoms and Covid-19. Dental professionals may encounter individuals with Covid-19 and be called upon to identify various oral manifestations of this disease.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Dysgeusia; Humans; Mouth Diseases; Mouth Mucosa; SARS-CoV-2; Taste Disorders; Xerostomia
PubMed: 34028129
DOI: 10.1002/rmv.2248 -
The New England Journal of Medicine Sep 2019Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Maribavir is a benzimidazole riboside with activity against cytomegalovirus (CMV). The safety and efficacy of maribavir for preemptive treatment of CMV infection in transplant recipients is not known.
METHODS
In a phase 2, open-label, maribavir dose-blinded trial, recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation [1000 to 100,000 DNA copies per milliliter]) were randomly assigned to receive maribavir at a dose of 400, 800, or 1200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks. The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment.
RESULTS
Of the 161 patients who underwent randomization, 159 received treatment, and 156 had postbaseline data available - 117 in the maribavir group and 39 in the valganciclovir group. The percentage of patients with postbaseline data available who had a response to treatment within 3 weeks was 62% among those who received maribavir and 56% among those who received valganciclovir. Within 6 weeks, 79% and 67% of patients, respectively, had a response (risk ratio, 1.20; 95% confidence interval, 0.95 to 1.51). The percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting maribavir at a dose of 800 mg twice daily; T409M resistance mutations in CMV UL97 protein kinase developed in both patients. The incidence of serious adverse events that occurred or worsened during treatment was higher in the maribavir group than in the valganciclovir group (52 of 119 patients [44%] vs. 13 of 40 [32%]). A greater percentage of patients in the maribavir group discontinued the trial medication because of an adverse event (27 of 119 [23%] vs. 5 of 40 [12%]). A higher incidence of gastrointestinal adverse events was reported with maribavir, and a higher incidence of neutropenia was reported with valganciclovir.
CONCLUSIONS
Maribavir at a dose of at least 400 mg twice daily had efficacy similar to that of valganciclovir for clearing CMV viremia among recipients of hematopoietic-cell or solid-organ transplants. A higher incidence of gastrointestinal adverse events - notably dysgeusia - and a lower incidence of neutropenia were found in the maribavir group. (Funded by ViroPharma/Shire Development; EudraCT number, 2010-024247-32.).
Topics: Adult; Aged; Allografts; Antiviral Agents; Benzimidazoles; Cytomegalovirus; Cytomegalovirus Infections; Dysgeusia; Female; Gastrointestinal Diseases; Hematopoietic Stem Cell Transplantation; Humans; Intention to Treat Analysis; Male; Middle Aged; Neutropenia; Organ Transplantation; Ribonucleosides; Valganciclovir; Viremia; Virus Activation
PubMed: 31532960
DOI: 10.1056/NEJMoa1714656 -
Cancer Radiotherapie : Journal de La... Jul 2021Purpose of this review of medical literature is to present the immediate side effects of radiation therapy for head and neck cancer and their treatment. The likelihood... (Review)
Review
Purpose of this review of medical literature is to present the immediate side effects of radiation therapy for head and neck cancer and their treatment. The likelihood and severity of these immediate side effects depends on a number of factors, including the total dose of radiation delivered, over what time it was delivered and what parts of the head and neck received radiation. Early side effects include: inflammation of the oropharyngeal mucosa (mucositis), painful swallowing (odynophagia), difficulty swallowing (dysphagia), hoarseness, lack of saliva (xerostomia), orofacial pain, laryngeal radionecrosis, dermatitis, hair loss, nausea, vomiting, inadequate nutrition and hydration, and weight loss. These complications can interfere with, and delay treatment. Most of these side effects generally dissipate over time. In conclusion, radiation treatment for the head and neck cancer causes significant early side effects. Many of these side effects present difficult challenges to the patients. Their recognition and treatment can significantly improve the patients' health, long-term survival and quality of life. The review provides information that can assist head and cancer survivors deal with radiation side effects.
Topics: Alopecia; Brain; Deglutition Disorders; Dehydration; Dysgeusia; Facial Pain; Fatigue; Head and Neck Neoplasms; Humans; Laryngeal Cartilages; Mouth Mucosa; Mucositis; Nausea; Necrosis; Periodontal Diseases; Radiodermatitis; Radiotherapy; Vomiting; Weight Loss; Xerostomia
PubMed: 33685809
DOI: 10.1016/j.canrad.2021.02.001 -
Journal of Indian Society of... 2022Since the advent of the coronavirus disease (COVID-19) infection, this highly infectious virus has spread worldwide infecting millions of people. Not only it has...
Since the advent of the coronavirus disease (COVID-19) infection, this highly infectious virus has spread worldwide infecting millions of people. Not only it has affected the pulmonary function of the body, leading to difficulty in breathing, but at the same time, an array of other systemic infections which may or may not be directly due to coronavirus infection, due to an absent established relationship. The mucocutaneous manifestations seen in COVID-19 infection include depapillation of the tongue, lesions seen on alveolar mucosa, gingiva, buccal mucosa, dysgeusia, and dry mouth. This case report highlights the effect of COVID-19 on the tongue also known as COVID tongue seen as depapillation of the tongue surface. Due to the absence of long-term studies and time-limited research, a direct relationship between COVID-19 and the systemic manifestation is not yet established. More research has to be done in this direction, to chart out the exact etiology of these systemic infections.
PubMed: 36339385
DOI: 10.4103/jisp.jisp_437_21 -
The New England Journal of Medicine Apr 2024Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-to-moderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-to-moderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients who are at standard risk for severe Covid-19 or who are fully vaccinated and have at least one risk factor for severe Covid-19 has not been established.
METHODS
In this phase 2-3 trial, we randomly assigned adults who had confirmed Covid-19 with symptom onset within the past 5 days in a 1:1 ratio to receive nirmatrelvir-ritonavir or placebo every 12 hours for 5 days. Patients who were fully vaccinated against Covid-19 and who had at least one risk factor for severe disease, as well as patients without such risk factors who had never been vaccinated against Covid-19 or had not been vaccinated within the previous year, were eligible for participation. Participants logged the presence and severity of prespecified Covid-19 signs and symptoms daily from day 1 through day 28. The primary end point was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Covid-19-related hospitalization and death from any cause were also assessed through day 28.
RESULTS
Among the 1296 participants who underwent randomization and were included in the full analysis population, 1288 received at least one dose of nirmatrelvir-ritonavir (654 participants) or placebo (634 participants) and had at least one postbaseline visit. The median time to sustained alleviation of all targeted signs and symptoms of Covid-19 was 12 days in the nirmatrelvir-ritonavir group and 13 days in the placebo group (P = 0.60). Five participants (0.8%) in the nirmatrelvir-ritonavir group and 10 (1.6%) in the placebo group were hospitalized for Covid-19 or died from any cause (difference, -0.8 percentage points; 95% confidence interval, -2.0 to 0.4). The percentages of participants with adverse events were similar in the two groups (25.8% with nirmatrelvir-ritonavir and 24.1% with placebo). In the nirmatrelvir-ritonavir group, the most commonly reported treatment-related adverse events were dysgeusia (in 5.8% of the participants) and diarrhea (in 2.1%).
CONCLUSIONS
The time to sustained alleviation of all signs and symptoms of Covid-19 did not differ significantly between participants who received nirmatrelvir-ritonavir and those who received placebo. (Supported by Pfizer; EPIC-SR ClinicalTrials.gov number, NCT05011513.).
Topics: Adult; Humans; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Diarrhea; Ambulatory Care; Dysgeusia; Vaccination; COVID-19 Vaccines
PubMed: 38598573
DOI: 10.1056/NEJMoa2309003 -
Neuropathology and Applied Neurobiology Apr 2024Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has... (Review)
Review
Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID-19-associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long-term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID-19-associated olfactory dysfunction.
Topics: Humans; COVID-19; SARS-CoV-2; Smell; Olfaction Disorders
PubMed: 38419211
DOI: 10.1111/nan.12960