Expert opinion on biological therapy
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Expert Opin Biol Ther · Aug 2021
An update on B-cell maturation antigen-targeted therapies in Multiple Myeloma.
Introduction: B-cell maturation antigen (BCMA) targeted therapy (BCMA-TT) has emerged as a promising treatment for Multiple Myeloma (MM). the three most common treatment modalities for targeting BCMA are antibody-drug conjugates (ADCs), bispecific antibody constructs, including BiTE (bispecific T-cell engager) immuno-oncology therapies, and chimeric antigen receptor (CAR)-modified T-cell therapy. Areas covered: The review provides an overview of the main published studies on clinical and pre-clinical data from trials using BCMA-TT. Expert opinion: Despite progresses in survival outcomes and the availability of new drugs, MM remains an incurable disease. ⋯ CAR-T cells produced unprecedented results in heavily pretreated RRMM. The most common toxicities include neurologic toxicity and cytokine release syndrome, B-cell aplasia, cytopenias, and hypogammaglobulinemia. Further studies are needed to detect which are the eligible patients who could benefit from one treatment more than another.
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Introduction: The therapeutic landscape of metastatic urothelial carcinoma (mUC) becomes increasingly dense: standard therapy remains cisplatin-based chemotherapy, followed by immunotherapy with checkpoint inhibitors as maintenance or second-line. New directions include erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor in patients with corresponding mutations in FGFR2/3 receptor. Enfortumab vedotin (EV) is an antibody-drug conjugate targeting nectin-4 and is conjugated with monomethyl auristatin E (MMAE). ⋯ Ongoing studies are explained, the present significance of the substance is assessed and its further future potential is outlined. Expert opinion Enfortumab vedotin has shown encouraging efficacy and a good tolerability in phase I/II trials, especially in heavily pretreated patients and patients with liver metastases. It appears to outperform third-line chemotherapies; ongoing studies will show the future potential of EV in treatment sequence.
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Expert Opin Biol Ther · Jul 2021
Targeting nectin-4 by antibody-drug conjugates for the treatment of urothelial carcinoma.
Nectin-4 is a tumor-associated antigen overexpressed in urothelial carcinoma and several other malignancies. It has emerged as a compelling target for novel tumor-directed therapies, particularly as a component of antibody-drug conjugates (ADCs), a growing class of anti-cancer therapeutic agents. Development of nectin-4-directed therapies has been led by enfortumab vedotin (EV), an ADC comprised of a fully human monoclonal antibody specific for nectin-4 conjugated via a cleavable linker to the microtubule inhibitor MMAE. EV was approved in 2019 as a first-in-class agent for the treatment of urothelial carcinoma. ⋯ EV offers proof-of-concept for the clinical utility of nectin-4-directed therapies and provides further support for ADCs as an important class of anti-cancer agents. Future development of nectin-4-targeted approaches will benefit from a deeper understanding of nectin-4 biology in both health and disease, as well as a detailed exploration of the mechanisms underlying therapeutic activity and resistance.
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Expert Opin Biol Ther · May 2021
Randomized Controlled Trial Multicenter StudyA two-arm, randomized, controlled, multi-centric, open-label phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19.
Objective: Efficacy and safety of Itolizumab, an immunomodulatory mAb, in treating moderate-to-severe acute respiratory distress syndrome (ARDS) due to cytokine release in COVID-19 patients was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase-2 study. Methods: Patients were randomized (2:1) to Arm-A (best supportive care [BSC]+Itolizumab) and Arm-B (BSC). Primary outcome of interest was reduction in mortality 30-days after enrollment. ⋯ At end of study, more patients in Arm-A had improved SpO2 without increasing FiO2 (p = 0.0296), improved PaO2 (p = 0.0296), and reduction in IL-6 (43 vs 212 pg/ml; p = 0.0296) and tumor necrotic factor-α (9 vs 39 pg/ml; p = 0.0253) levels. Transient lymphopenia (Arm-A: 11 patients) and infusion reactions (7 patients) were commonly reported treatment-related safety events. Conclusion: Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit.
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Expert Opin Biol Ther · May 2021
Dupilumab for the treatment of chronic rhinosinusitis with nasal polyposis.
Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) affects 1-2.5% of the population and is associated with significant adverse effects on quality of life (QoL). CRSwNP is strongly correlated with (late onset) asthma with 30-70% of the CRSwNP patients having asthma. Health-care spending in rhinosinusitis is high, especially because of indirect costs. ⋯ Treatment with dupilumab results in a significant improvement of QoL (measured as SNOT-22), rhinosinusitis disease severity, symptoms of rhinosinusitis, and especially sense of smell, nasal polyp score, Lund-Mackay CT score, and asthma outcomes (ACQ5 and FEV1) compared to placebo. Expert opinion: At this moment, the high cost of the treatment requires careful patient selection and within the EUFOREA and EPOS2020 context, experts have tried to give guidance based on today's data. We now need trials evaluating which patients benefit most from treatment with biologicals and in which patients the treatment is cost-effective.