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Hematology/oncology Clinics of North... Apr 2024Despite improved treatments, most patients with multiple myeloma (MM) will experience relapse. Several novel agents have demonstrated activity and tolerability in early... (Review)
Review
Despite improved treatments, most patients with multiple myeloma (MM) will experience relapse. Several novel agents have demonstrated activity and tolerability in early phase clinical trials. Venetoclax is a B-cell lymphoma 2 (Bcl-2) inhibitor with activity in patients with t(11;14) and/or Bcl-2 expression. Iberdomide and mezigdomide are cereblon E3 ligase modulators with higher potency, immunomodulatory, and antiproliferative activity compared with lenalidomide and pomalidomide. They have shown promising activity in heavily pretreated patients. Modakafusp alfa is an immunocytokine that targets interferons to CD38+ cells. It has demonstrated single agent activity in relapsed/refractory MM in the phase 1 setting.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Antineoplastic Agents; Lenalidomide; Proto-Oncogene Proteins c-bcl-2; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38216384
DOI: 10.1016/j.hoc.2023.12.013 -
Clinical Lymphoma, Myeloma & Leukemia Dec 2023Dose modifications in response to adverse events (AEs) can maintain tumor response and improve therapy tolerability. We conducted a post-hoc analysis of the efficacy and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Dose modifications in response to adverse events (AEs) can maintain tumor response and improve therapy tolerability. We conducted a post-hoc analysis of the efficacy and safety of reduced selinexor doses in the BOSTON trial (NCT03110562).
PATIENTS AND METHODS
Efficacy, safety, and quality of life (QoL) in 195 patients with relapsed/refractory multiple myeloma randomized to once-weekly (QW) selinexor (100 mg), QW subcutaneous bortezomib (1.3 mg/m), and twice-weekly dexamethasone (20 mg) were compared between patients with dose reductions and those without.
RESULTS
In total, 126 patients (65%) had selinexor dose reductions (median dose 71.4 mg/wk). In patients with dose reductions versus those without median progression-free survival was 16.6 months (95% CI 12.9-not evaluable [NE]) versus 9.2 months [95% CI 6.8-15.5]), overall response rate was 81.7% (95% CI 73.9-88.1%) versus 66.7% (95% CI 54.3-77.6%), ≥very good partial response was (51.6% [95% CI 42.5-60.6%] vs. 31.9% [95% CI 21.2-44.2]), median duration of response was not reached (95% CI 13.8-NE) versus 12.0 months (95% CI 8.3-NE), and time to next treatment was 22.6 months (95% CI 14.6-NE) versus 10.5 months (95% CI 6.3-18.2). Mean best change from baseline on the EORTC QLQ-C30 Global Health Status/QoL scale was 10.0 ± 20.5 versus 4.0 ± 20.9. Duration-adjusted AE rates that were lower after selinexor dose reduction included thrombocytopenia (62.5% before vs. 47.6% after), nausea (31.6% vs. 7.3%), fatigue (28.1% vs. 9.9%), decreased appetite (21.5% vs. 6.4%), anemia (17.9% vs. 10.3%), and diarrhea (12.9% vs. 5.2%).
CONCLUSION
Appropriate dose reductions in response to AEs of the 100 mg selinexor starting dose in the BOSTON study were associated with improved efficacy, reduced AE rates and improved QoL.
Topics: Humans; Quality of Life; Drug Tapering; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Multiple Myeloma
PubMed: 37743180
DOI: 10.1016/j.clml.2023.08.018 -
International Ophthalmology Nov 2023We aim to contribute to the literature in terms of treatment safety with our real world data by examining the anterior segment complications and follow-up results of...
PURPOSE
We aim to contribute to the literature in terms of treatment safety with our real world data by examining the anterior segment complications and follow-up results of patients who underwent dexamethasone implants in our clinic.
METHODS
The records of patients treated with at least one intravitreal dexamethasone implant for various retinal diseases: diabetic macular edema (265 eyes), central retinal vein occlusion (45 eyes), retinal vein branch occlusion (91 eyes), postoperative cystoid macular edema (18 eyes), non-infectious uveitis (37 eyes) and other (14 eyes) between July 2013 and April 2020 were reviewed.
RESULTS
After 925 injections were applied to 470 eyes of a total of 383 patients, the eyes were controlled during a mean follow-up of 24 months. No complications were detected in 328 eyes. Intraocular pressure (IOP) above 25 mmHg was detected in 97 eyes (20.6%) that had no previous history of ocular hypertension. Of these 97 eyes, 71 (73.1%) eyes with increased IOP were treated with topical monotherapy, 26 (26.8%) eyes were treated with topical combined therapy and 1 (1.03%) patient had glaucoma surgery. Cataracts requiring surgical intervention developed in 55 (%21.73) of 253 phakic eyes. Three patients have anterior chamber dislocation of dexamethasone, 1 patient was hospitalized with sterile endophthalmitis on the 7th day after the injection, and pars plana vitrectomy was performed.
CONCLUSION
This study is the first long-term follow-up study in our country evaluating the safety of dexamethasone implant injections in various retinal diseases and presenting the first real world data. Cataract progression and increased IOP were found to be the most common side effects. We observed that the patient's diagnosis did not cause a statistically significant change in the observation of side effects. As a result of our findings, close follow-up of IOP after the injection of dexamethasone implants would be appropriate.
Topics: Humans; Diabetic Retinopathy; Follow-Up Studies; Macular Edema; Cataract; Retinal Vein Occlusion; Retinal Diseases; Anterior Chamber; Dexamethasone
PubMed: 37707746
DOI: 10.1007/s10792-023-02838-4 -
Indian Journal of Ophthalmology Jan 2024Our aim was to identify recent research trends on diabetic macular edema (DME) and focus on publications from different countries, institutions, and authors.
PURPOSE
Our aim was to identify recent research trends on diabetic macular edema (DME) and focus on publications from different countries, institutions, and authors.
METHODS
We retrieved and analyzed data from January 1, 2003 to December 31, 2022 on the DME research field from the Web of Science Core Collection (WoSCC) database. Microsoft Excel and VOSviewer were applied to perform visualization analysis and evaluate the trends.
RESULTS
A total of 4482 publications were identified, and the annual global publications increased steadily, from 36 to 390, during this period. The United States (1339 publications, 71,754 citations), Johns Hopkins University (176 publications, 17,015 citations), and Bressler NM (76 publications, 9621 citations) were the most influential and productive countries, institutions, and authors, respectively. The top 100 keywords were classified into five clusters: (1) therapy and adverse effects of DME; (2) clinical biomarkers of DME; (3) mechanistic research on DME; (4) improving bioavailability and efficacy; and (5) early diagnosis of diabetic complications. "Diabetic macular edema," "retinopathy," "ranibizumab," and "optical coherence tomography angiography" were the most frequent keywords. Regarding the average appearing years (AAYs) of the keywords, "deep learning" (AAY:2020.83), "optical coherence tomography angiography" (AAY:2019.59), "intravitreal Aflibercept" (AAY:2019.29), and "dexamethasone implant" (AAY:2019.20) were recognized as the hotspots of the DME research area in the short run.
CONCLUSION
In the past two decades, the United States was in master status in DME research. Although intravitreal drug injection has been the mainstream therapy for a long time, the effectiveness of different drugs, such as dexamethasone, new solutions for drug delivery, such as intravitreal implantation, and more accurate tools for the classification and follow-up of DME patients, such as deep learning systems, are still research hotspots.
Topics: Humans; Macular Edema; Diabetic Retinopathy; Ranibizumab; Tomography, Optical Coherence; Bibliometrics; Dexamethasone; Intravitreal Injections; Diabetes Mellitus
PubMed: 38131545
DOI: 10.4103/IJO.IJO_399_23 -
Stem Cell Research & Therapy Aug 2023High dosage of dexamethasone (Dex) is an effective treatment for multiple diseases; however, it is often associated with severe side effects including muscle atrophy,...
BACKGROUND
High dosage of dexamethasone (Dex) is an effective treatment for multiple diseases; however, it is often associated with severe side effects including muscle atrophy, resulting in higher risk of falls and poorer life quality of patients. Cell therapy with mesenchymal stem cells (MSCs) holds promise for regenerative medicine. In this study, we aimed to investigate the therapeutic efficacy of systemic administration of adipose-derived mesenchymal stem cells (ADSCs) in mitigating the loss of muscle mass and strength in mouse model of DEX-induced muscle atrophy.
METHODS
3-month-old female C57BL/6 mice were treated with Dex (20 mg/kg body weight, i.p.) for 10 days to induce muscle atrophy, then subjected to intravenous injection of a single dose of ADSCs ([Formula: see text] cells/kg body weight) or vehicle control. The mice were killed 7 days after ADSCs treatment. Body compositions were measured by animal DXA, gastrocnemius muscle was isolated for ex vivo muscle functional test, histological assessment and Western blot, while tibialis anterior muscles were isolated for RNA-sequencing and qPCR. For in vitro study, C2C12 myoblast cells were cultured under myogenic differentiation medium for 5 days following 100 [Formula: see text]M Dex treatment with or without ADSC-conditioned medium for another 4 days. Samples were collected for qPCR analysis and Western blot analysis. Myotube morphology was measured by myosin heavy chain immunofluorescence staining.
RESULTS
ADSC treatment significantly increased body lean mass (10-20%), muscle wet weight (15-30%) and cross-sectional area (CSA) (~ 33%) in DEX-induced muscle atrophy mice model and down-regulated muscle atrophy-associated genes expression (45-65%). Hindlimb grip strength (~ 37%) and forelimb ex vivo muscle contraction property were significantly improved (~ 57%) in the treatment group. Significant increase in type I fibres (~ 77%) was found after ADSC injection. RNA-sequencing results suggested that ERK1/2 signalling pathway might be playing important role underlying the beneficial effect of ADSC treatment, which was confirmed by ERK1/2 inhibitor both in vitro and in vivo.
CONCLUSIONS
ADSCs restore the pathogenesis of Dex-induced muscle atrophy with an increased number of type I fibres, stronger muscle strength, faster recovery rate and more anti-fatigue ability via ERK1/2 signalling pathway. The inhibition of muscle atrophy-associated genes by ADSCs offered this treatment as an intervention option for muscle-associated diseases. Taken together, our findings suggested that adipose-derived mesenchymal stem cell therapy could be a new treatment option for patient with Dex-induced muscle atrophy.
Topics: Mice; Female; Animals; MAP Kinase Signaling System; Mice, Inbred C57BL; Muscular Atrophy; Muscle, Skeletal; Mesenchymal Stem Cells; Dexamethasone; Body Weight; RNA
PubMed: 37542297
DOI: 10.1186/s13287-023-03418-0 -
BMJ Supportive & Palliative Care Jan 2024Dexamethasone causes hiccups in an undefined percentage of patients, and these hiccups are often ignored ('My doctors just shook their heads like I was joking …')....
OBJECTIVES
Dexamethasone causes hiccups in an undefined percentage of patients, and these hiccups are often ignored ('My doctors just shook their heads like I was joking …'). This study sought to learn the percentage of dexamethasone-treated patients who develop hiccups and to explore patients' responses to the availability of educational materials on hiccups.
METHODS
English-speaking, adult outpatients treated with oral, intravenous or epidural dexamethasone 2 weeks prior were contacted by phone and asked about hiccups. Educational materials were offered, and patients were queried on their opinion of the availability of such materials.
RESULTS
One hundred and twenty-seven patients or 11% (95% CI 9% to 13%) reported hiccups. This percentage was derived from 1186 reachable patients from 2000 total patients. Fifty-four (43%) of those with hiccups desired to learn about educational materials. Of these, 49 completed a single-item, 5-point scale item: 21 (43%) viewed the availability of educational materials 'extremely helpful,' providing a 5 rating; 8 (16%) provided a 4; 4 (8%) provided a 3; and 1 (4%) provided a 2.
CONCLUSIONS
Dexamethasone-induced hiccups occur in a small percentage of patients. The fact that most patients responded favourably to learning about the availability of educational materials suggests some have unmet needs.
Topics: Adult; Humans; Dexamethasone; Hiccup
PubMed: 34903586
DOI: 10.1136/bmjspcare-2021-003474 -
Anaesthesia Dec 2023The effects of oral dexamethasone on peripheral nerve blocks have not been investigated. We randomly allocated adults scheduled for forearm or hand surgery to oral... (Randomized Controlled Trial)
Randomized Controlled Trial
The effects of oral dexamethasone on peripheral nerve blocks have not been investigated. We randomly allocated adults scheduled for forearm or hand surgery to oral placebo (n = 61), dexamethasone 12 mg (n = 61) or dexamethasone 24 mg (n = 57) about 45 min before lateral infraclavicular block. Mean (SD) time until first pain after block were: 841 (327) min; 1171 (318) min; and 1256 (395) min, respectively. Mean (98.3%CI) differences in time until first postoperative pain for dexamethasone 24 mg vs. placebo and vs. dexamethasone 12 mg were: 412 (248-577) min, p < 0.001; and 85 (-78 to 249) min, p = 0.21, respectively. Mean (98.3%CI) difference in time until first postoperative pain for dexamethasone 12 mg vs. placebo was 330 (186-474) min, p < 0.001. Both 24 mg and 12 mg of oral dexamethasone increased the time until first postoperative pain compared with placebo in patients having upper limb surgery under infraclavicular brachial plexus block.
Topics: Adult; Humans; Brachial Plexus Block; Dexamethasone; Pain, Postoperative; Analgesia; Upper Extremity; Anesthetics, Local
PubMed: 37864459
DOI: 10.1111/anae.16149 -
Molecular Pharmaceutics Aug 2023We undertook this study to investigate the effects and mechanisms of dexamethasone liposome (Dex-Lips) on alleviating destabilization of the medial meniscus...
We undertook this study to investigate the effects and mechanisms of dexamethasone liposome (Dex-Lips) on alleviating destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) in miR-204/-211-deficient mice. Dex-Lips was prepared by the thin-film hydration method. The characterization of Dex-Lips was identified by the mean size, zeta potential, drug loading, and encapsulation efficiencies. Experimental OA was established by DMM surgery in miR-204/-211-deficient mice, and then Dex-Lips was treated once a week for 3 months. Von Frey filaments was used to perform the pain test. The inflammation level was evaluated with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Polarization of macrophages was evaluated by immunofluorescent staining. X-ray, micro-CT scanning, and histological observations were conducted in vivo on DMM mice to describe the OA phenotype. We found that miR-204/-211-deficient mice displayed more severe OA symptoms than WT mice after DMM surgery. Dex-Lips ameliorated DMM-induced OA phenotype and suppressed pain and inflammatory cytokine expressions. Dex-Lips could attenuate pain by regulating PGE2. Dex-Lips treatments reduced the expression of TNF-α, IL-1β, and IL-6 in DRG. Moreover, Dex-Lips could reduce inflammation in the cartilage and serum. Additionally, Dex-Lips repolarize synovial macrophages to M2 phenotypes in miR-204/-211-deficient mice. In conclusion, Dex-Lips inhibited the inflammatory response and alleviated the pain symptoms of OA by affecting the polarization of macrophages.
Topics: Mice; Animals; Liposomes; Osteoarthritis; Inflammation; Pain; Dexamethasone; Macrophages; MicroRNAs; Disease Models, Animal
PubMed: 37437059
DOI: 10.1021/acs.molpharmaceut.2c00979 -
Journal of Oncology Pharmacy Practice :... Jan 2024Elotuzumab in combination with dexamethasone and immunomodulating agents (IMiDs) lenalidomide or pomalidomide is 2nd to 4th line therapy for multiple myeloma. The...
Elotuzumab in combination with dexamethasone and immunomodulating agents (IMiDs) lenalidomide or pomalidomide is 2nd to 4th line therapy for multiple myeloma. The labelled dosage of dexamethasone for use in conjunction with elotuzumab and IMiDs splits the dexamethasone dose into two administrations, one oral and one intravenous, on the days of each elotuzumab infusion. Administration of split dose dexamethasone on days of elotuzumab administration is based on the registration trials submitted for drug approval and was intended to ensure standard well-timed immunotherapy premedication using pharmacologically equivalent dexamethasone doses for both study arms. Administration of dexamethasone in the manner delineated by the elotuzumab product label adds complexity to the delivery of care. This commentary provides an empirical assessment of established medication safety and effectiveness which supports administration of dexamethasone standard intermittent dose instead of the split dose approach delineated on elotuzumab package insert. Simplification of regimen administration improves medication adherence, reduces the risk of inadvertent omission or duplication of medication therapy, and improves the workflow required for delivery of care.
Topics: Humans; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Multiple Myeloma; Immunomodulating Agents; Antibodies, Monoclonal, Humanized
PubMed: 37876226
DOI: 10.1177/10781552231207855 -
European Journal of Pharmaceutics and... May 2024Even though subconjunctival injections are used in clinics, their quantitative pharmacokinetics has not been studied systematically. For this purpose, we evaluated the...
Even though subconjunctival injections are used in clinics, their quantitative pharmacokinetics has not been studied systematically. For this purpose, we evaluated the ocular and plasma pharmacokinetics of subconjunctival dexamethasone in rabbits. Intravenous injection was also given to enable a better understanding of the systemic pharmacokinetics. Dexamethasone concentrations in plasma (after subconjunctival and intravenous injections) and four ocular tissues (iris-ciliary body, aqueous humour, neural retina and vitreous) were analysed using LC-MS/MS. Population pharmacokinetic modelling for plasma data from both injection routes were used, and for first time the constant rate of absorption of dexamethasone from the subconjunctival space into plasma was estimated (k = 0.043 min, i.e. absorption half-life of 17.3 min). Non-compartmental analysis was used for the ocular data analysis and resulting in ocular drug exposure of iris-ciliary body (AUC= 41984 min·ng/g) > neural retina (AUC= 25511 min·ng/g) > vitreous (AUC= 7319 min·ng/mL) > aqueous humour (AUC= 6146 min·ng/mL). The absolute bioavailability values after subconjunctival injection, reported for the first time, were 0.74 % in aqueous humour (comparable to topical dexamethasone suspensions), and 0.30 % in vitreous humour (estimated to be higher than in topical administration). These novel and comprehensive pharmacokinetic data provide valuable information on the potential for exploiting this route in ocular drug development for treating both, anterior and posterior segment ocular diseases. Moreover, the new generated dexamethasone-parameters are a step-forward in building predictive pharmacokinetic models to support the design of new subconjunctival dexamethasone formulations, which may sustain drug effect for longer period of time.
Topics: Animals; Rabbits; Injections, Intravenous; Chromatography, Liquid; Tandem Mass Spectrometry; Vitreous Body; Dexamethasone
PubMed: 38484852
DOI: 10.1016/j.ejpb.2024.114260