INTRODUCTION: Bispecific antibodies (bsAbs) have demonstrated impressive standalone effectiveness in relapsed and refractory multiple myeloma, as evidenced by clinical trials and real-world findings. Current clinical stu...INTRODUCTION: Bispecific antibodies (bsAbs) have demonstrated impressive standalone effectiveness in relapsed and refractory multiple myeloma, as evidenced by clinical trials and real-world findings. Current clinical studies are investigating these drugs as both monotherapies and in combination treatments for earlier stages of myeloma, including newly diagnosed cases. AREAS COVERED: With many options available in clinical settings, several questions emerge: How can one bsAb be chosen over another? What is the best way to administer bsAbs, including initial step-up and continuous dosing schedules? How can unique toxicities be managed, and what strategies should be used to address disease relapses following bsAb treatment? EXPERT OPINION: Tocilizumab is being investigated in the prevention of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Steroids can be used to safely treat CRS in myeloma patients on bsAb therapy. This may allow a safe outpatient step-up dosing program. Despite improved infection management with intravenous immunoglobulin prophylaxis, infection risks continue as long as patients are on therapy. This indicates alternative strategies like less frequent dosing or finite duration therapy are needed. Optimal management of disease relapse after bsAb therapy and the sequencing of bsAb and chimeric antigen receptor (CAR) T-cell therapies require further investigation.
BACKGROUND: Efgartigimod for intravenous infusion (efgartigimod-IV) is approved in Japan for generalized myasthenia gravis (gMG). Post-marketing surveillance was mandated by regulatory authorities to assess the safety an...BACKGROUND: Efgartigimod for intravenous infusion (efgartigimod-IV) is approved in Japan for generalized myasthenia gravis (gMG). Post-marketing surveillance was mandated by regulatory authorities to assess the safety and effectiveness of efgartigimod in patients with gMG. RESEARCH DESIGN AND METHODS: Patients with gMG who received efgartigimod-IV between May 2022 and September 2023 were registered. The interim analysis data were cutoff in June 2024 and included patients whose institutions agreed to publication. RESULTS: The safety analysis set consisted of 373 patients: 53.35% ( = 199) anti-acetylcholine receptor antibody positive, 14.21% ( = 53) anti-muscle-specific receptor kinase antibody positive, and 31.64% ( = 118) double-seronegative. Adverse drug reaction and serious adverse drug reaction were reported in 21.45% (80/373) and 4.29% (16/373) of patients, respectively. Although six deaths were reported, none of them were related to efgartigimod. The effectiveness analysis set consisted of 246 patients. After three weeks from the first administration, mean score of MG-Activities of Daily Living decreased from 7.5 to 4.4: -3.1 points improvement (standard deviation: 2.95, < 0.001). No remarkable differences were observed in the response to efgartigimod between the subgroups of patient baseline characteristics, e.g. autoantibody profiles. CONCLUSIONS: In real-world settings, efgartigimod-IV was well tolerated and effective in patients with gMG.
BACKGROUND: There may be patient concerns with switching to a biosimilar product. The purpose of this study was to describe the perspectives of patients with inflammatory bowel disease (IBD) after switching from referenc...BACKGROUND: There may be patient concerns with switching to a biosimilar product. The purpose of this study was to describe the perspectives of patients with inflammatory bowel disease (IBD) after switching from reference product (RP) adalimumab to adalimumab-atto. RESEARCH DESIGN AND METHODS: This was a telephonic survey of US patients with IBD conducted in June-July 2023 among adult, English-speaking patients who were switched to biosimilar adalimumab-atto from RP adalimumab within the previous 100 days, and were receiving adalimumab-atto at the time of the survey. Consented participants were queried on adalimumab-atto safety and effectiveness, cost, product preference, and education received for the switch. Descriptive statistics were used to depict responses. RESULTS: Of the 250 patients contacted, 154 participants completed the survey. Respondents (77.9%) reported no concerns with loss of disease control, potential side effects (67.9%), or cost (89.5%) after switching. About 28.7% reported a preference for adalimumab-atto, while 39.3% reported no preference between products. About 43.7% reported being satisfied/very satisfied with the education they received, while 65.1% stated they did not feel they knew enough about adalimumab-atto. CONCLUSIONS: There was widespread satisfaction with adalimumab-atto after switching from RP adalimumab. Nevertheless, participants reported limited knowledge of adalimumab-atto, suggesting a need for enhanced education on biosimilars.
INTRODUCTION: Immunotherapy combined with anti-angiogenesis has become a useful strategy in cancer treatment. Ivonescimab, the first-approved bispecific antibody targeting both immune checkpoint inhibition and anti-angio...INTRODUCTION: Immunotherapy combined with anti-angiogenesis has become a useful strategy in cancer treatment. Ivonescimab, the first-approved bispecific antibody targeting both immune checkpoint inhibition and anti-angiogenesis, represents a breakthrough over the conventional dual-drug combination approach. The emerging clinical evidence demonstrates promising efficacy and manageable safety profile of ivonescimab in the treatment of non-small cell lung cancer (NSCLC), suggesting its potential role as a cornerstone in the next generation of cancer immunotherapy. AREAS COVERED: This review presents the pharmacological characteristics of ivonescimab, revisits relevant clinical trials and key data, and provides an in-depth analysis. Additionally, the potential of ivonescimab in NSCLC treatment is discussed, along with its clinical prospects. EXPERT OPINION: The available clinical data demonstrate that simultaneously targeting both immune checkpoint inhibition and angiogenesis pathways through a single bispecific antibody represents a significant therapeutic advancement in NSCLC treatment. Ivonescimab's innovative dual-targeting mechanism, supported by promising efficacy data from the HARMONi trials and its manageable safety profile, appears to be fundamental to its potential to challenge current standards of care. As the first approved bispecific antibody with this unique mechanism of action, ivonescimab may not only transform current treatment paradigms but also pioneer a new direction in cancer immunotherapy.
INTRODUCTION: Melanoma is among the most immunogenic malignancies. The advent of immune checkpoint inhibitors (ICIs) has revolutionized the landscape of melanoma treatment. Long-term durable cancer control is possible in...INTRODUCTION: Melanoma is among the most immunogenic malignancies. The advent of immune checkpoint inhibitors (ICIs) has revolutionized the landscape of melanoma treatment. Long-term durable cancer control is possible in nearly 50% of non-resectable, metastatic melanoma patients with anti-CTLA4 and anti-PD-1 antibodies. AREAS COVERED: This review provides a critical overview of the current data and future research directions on the management of metastatic melanoma with ICIs. We reviewed the efficacy and safety of combinations with PD-1 inhibitors through PubMed database research (Nov 2024-Mar 2025). EXPERT OPINION: A decade after ipilimumab's approval, challenges remain. To cure more patients, the development of combinations is warranted. Combinations with a limited number of ipilimumab applications improve the overall survival outcome by approximately 10%, with a dramatic increase in adverse events including fatal events. Anti-LAG3/nivolumab is a promising alternative, offering similar efficacy to ipilimumab/nivolumab with better tolerability. In our opinion, ipilimumab/nivolumab combination should be the first-line therapy for high-risk patients (high LDH, brain or liver metastasis), while nivolumab/relatlimab or PD-1 monotherapy may be preferable for lower-risk cases. However, treatment decisions are increasingly complex, since most patients nowadays are pretreated in the (neo)-adjuvant setting. The key limitation today is the lack of biomarkers to guide individualized treatment strategies.
INTRODUCTION: The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin...INTRODUCTION: The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases. AREAS COVERED: Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed. EXPERT OPINION: In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.
INTRODUCTION: Systemic adjuvant therapy is indicated in patients with high-risk, resected melanoma to reduce recurrence risk and potentially improve survival rates. Monoclonal antibodies (mAbs) target immune checkpoints...INTRODUCTION: Systemic adjuvant therapy is indicated in patients with high-risk, resected melanoma to reduce recurrence risk and potentially improve survival rates. Monoclonal antibodies (mAbs) target immune checkpoints and have made significant advances as systemic adjuvant therapies. AREAS COVERED: This review discusses the main clinical trials that tested adjuvant mAbs in resected high-risk melanoma, including anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1); in addition to newer immunotherapies being tested in the adjuvant setting, including anti-lymphocyte activation gene 3 (LAG-3). We also briefly discuss targeted therapies as an alternative choice. Moreover, we highlight the pros and cons of using mAbs in the adjuvant setting, the reported adverse events (AEs), and the quality of life impact. Finally, we report data related to biomarker studies tested in the context of these clinical trials. EXPERT OPINION: Immune checkpoint inhibitors (ICIs) have been shown to significantly improve relapse-free survival (RFS) as adjuvant therapy for high-risk melanoma. The long-term impact on overall survival (OS) was demonstrated in two trials that tested ipilimumab as compared to placebo (EORTC18071) and interferon-α (ECOG-ACRIN E1609). Furthermore, emerging data with neoadjuvant therapy followed by surgery and adjuvant therapy utilizing ICIs have demonstrated improved outcomes in the management of locoregionally advanced disease when compared to upfront surgery followed by adjuvant therapy alone.
BACKGROUND: The aim of this study is to confront the effectiveness of anti-IL 17 versus anti-IL 23 mAb in treating palmoplantar psoriasis by comparing the incidence of patients that required a therapy switch to another m...BACKGROUND: The aim of this study is to confront the effectiveness of anti-IL 17 versus anti-IL 23 mAb in treating palmoplantar psoriasis by comparing the incidence of patients that required a therapy switch to another mAb class. Furthermore, we calculated the mean time intercurrent the beginning therapy with mAbs and the necessity to switch class due to ineffectiveness. RESEARCH DESIGN AND METHODS: We enrolled 116 patients with moderate to severe palmoplantar psoriasis. Patients with the pustular variant were excluded from this study. We performed statistical analysis to calculate the incidence of therapy switch in anti-IL 17 and anti-IL 23 mAb therapies. RESULTS: The results of both univariate and multivariate statistical analysis demonstrated that patients in therapy with anti-IL 23 mAb have a lower incidence of therapy switch compared to patients in therapy with anti-IL 17 drugs. The median switch time is 105 months. No other significant factors predictive of therapy switch were found. CONCLUSIONS: This real-life evidence confirms the reduced necessity of therapy switch in patients with palmoplantar psoriasis treated with anti-IL 23 antibodies, compared to those treated with IL 17 inhibitors.
INTRODUCTION: Patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) have a poor median survival rate when treated with traditional salvage therapies. Bispecific antibodies (BsAbs) are an emerging class of...INTRODUCTION: Patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) have a poor median survival rate when treated with traditional salvage therapies. Bispecific antibodies (BsAbs) are an emerging class of 'off-the-shelf' immunotherapies that show promising efficacy in this population. Odronextamab is a CD20×CD3 targeting bispecific antibody that is being investigated in multiple subtypes of relapsed/refractory B-NHL. AREAS COVERED: This article describes the development of odronextamab from pre-clinical work through to ongoing clinical trials in relapsed/refractory B-NHL. The structure, safety, efficacy, and administration of odronextamab are discussed. Studies were selected for inclusion by performing a search in PubMed, EMBASE, Cochrane Library, and relevant conference abstracts from 2014 to 2024. The clinicaltrials.gov website and reference lists of the included studies were also reviewed. EXPERT OPINION: Odronextamab has demonstrated manageable safety and promising efficacy in multiple subtypes of relapsed/refractory B-NHL. The low rates of immune effector cell-associated neurotoxicity syndrome (ICANS) and high response rates in rare aggressive subtypes of B-NHL are particularly noteworthy. High rates of severe infections remain a challenge with BsAbs, with further prophylactic efforts required to reduce the risk. Clinical trials of combination therapies with odronextamab are required to improve the utility of this BsAb across a wider range of settings and subtypes of B-NHL.
INTRODUCTION: Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory bowel disease. Monoclonal antibodies targeting interleukin (IL)-23p19 have been developed to treat chronic inflammatory diseases m...INTRODUCTION: Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory bowel disease. Monoclonal antibodies targeting interleukin (IL)-23p19 have been developed to treat chronic inflammatory diseases mediated by aberrant IL23/Th17 responses, including psoriasis, psoriatic arthritis, and Crohn's disease. More recently, these agents have been evaluated for the treatment of moderately-to-severely active UC. AREAS COVERED: In this review, we summarize and discuss phase 2 and pivotal phase 3 clinical trials informing the efficacy and safety of mirikizumab (AMAC, LUCENT, and SHINE), risankizumab (INSPIRE, COMMAND), and guselkumab (QUASAR, VEGA). The literature search included original research publications, secondary publications, and preliminary data from conference abstracts presented at international gastroenterology meetings from the past 5 years. EXPERT OPINION: The approval of IL23p19 antagonists expands the armamentarium of effective and safe therapies for patients living with moderately-to-severely active UC. These agents demonstrate potent efficacy for both inducing and maintaining symptomatic and objective disease endpoints, including endoscopic, histologic, and biomarker remission. These well-tolerated agents are effective in both advanced treatment-naïve and experienced patients. Accordingly, IL23p19 antagonists have the potential to be used in a diverse population of patients with UC, and as potential platform therapies for future combinations with other targeted immunomodulatory agents.
INTRODUCTION: Belimumab (BEL), an anti B-lymphocyte stimulator monoclonal antibody, is the only approved biological therapy for systemic lupus erythematosus (SLE) and lupus nephritis (LN). AREAS COVERED: This review disc...INTRODUCTION: Belimumab (BEL), an anti B-lymphocyte stimulator monoclonal antibody, is the only approved biological therapy for systemic lupus erythematosus (SLE) and lupus nephritis (LN). AREAS COVERED: This review discusses BEL's real-world use and its positioning in clinical practice guidelines, focusing on the evolution of its application and patient profile over the last decade in Spain. EXPERT OPINION: Initially used for refractory and non-major SLE manifestations, BEL's application has expanded. International guidelines now recommend earlier use of BEL in treatment algorithms. With its 2021 approval for LN, BEL is increasingly used for renal manifestations and as a first-line therapy. Safety data confirm its tolerability without a significant increase in severe infections. However, real-world evidence in Spain reveals discrepancies with these recommendations for both SLE and LN. The optimal patient for BEL treatment is one with mild, moderate, or severe SLE that cannot be controlled with hydroxychloroquine (HCQ), with or without glucocorticoids (GC) and immunosuppressants (IS), in patients with a disease duration of ≤2 years, no initial organ damage, GC doses ≥5 mg/day, and a high risk of severe flares. Further studies are needed to determine the optimal timing for BEL initiation to improve patient outcomes and modify the disease course.
INTRODUCTION: Antibody-based immunotherapies are a class of therapeutics under active investigation in clinical trials for the treatment of acute myeloid leukemia (AML). Our review provides a comprehensive examination of...INTRODUCTION: Antibody-based immunotherapies are a class of therapeutics under active investigation in clinical trials for the treatment of acute myeloid leukemia (AML). Our review provides a comprehensive examination of trials published to date, focusing on recurrent challenges and promising aspects of antibody-based therapeutics. AREAS COVERED: We described antibody-based immunotherapies for AML, specifically, an overview of the most prominent antigen targets in published clinical trials investigating monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor therapies. Manuscripts and abstracts describing clinical trials investigating antibody-based therapies for AML published through December 2024, identified by searching Google Scholar and PubMed, were included. EXPERT OPINION: Antibody-based immunotherapies for AML have encountered limitations, including imperfect target antigens with significant associated toxicity such as myelosuppression, in addition to challenges specific to the AML patient population. The majority of trials have targeted CD33, CD123, CD371 (CLL1/Clec12), and CD47. For successful implementation of antibody-based therapeutics in AML treatment, future directions require creative applications of antibody-based therapeutics specifically engineered to minimize limiting toxicities and tailoring of therapies for this unique patient population.
INTRODUCTION: Adding monoclonal antibodies to chemotherapy drastically changed the landscape of advanced colorectal cancer. The prediction of benefit from anti-EGFR therapies is mainly based on the absence of mutations i...INTRODUCTION: Adding monoclonal antibodies to chemotherapy drastically changed the landscape of advanced colorectal cancer. The prediction of benefit from anti-EGFR therapies is mainly based on the absence of mutations in RAS and BRAF genes, the primary tumor sidedness and microsatellite MSS/MSI status. Molecular hyperselection may optimize the outcome of patients receiving anti-EGFR while detecting additional resistance alterations, both in chemo-naïve and in chemo-refractory settings. AREAS COVERED: Our review focuses on negative molecular hyperselection, both on tissue samples and ctDNA, and the impact of this further patient selection on response rate and survival outcomes. We searched electronic database, selecting relevant English-language publications from 2017 to 2024. EXPERT OPINION: Negative hyperselection beyond RAS and BRAF in advanced colorectal cancer appears to be a powerful tool for predicting outcomes to anti-EGFR therapy and spare patients from unnecessary treatment. This improvement appears in both naïve and pre-treated patients. However, data come mainly from retrospective studies. Therefore, to validate and integrate these findings in the clinical practice, prospective studies should be conducted. It will be interesting to elucidate the role of ctDNA in this setting and the choice of molecular techniques, considering costs and accessibility, to guarantee its implementation in the clinic.
INTRODUCTION: X-linked myotubular myopathy (XLMTM) is a life-threatening congenital disorder characterized by severe respiratory and motor impairment. This disease presents significant therapeutic challenges, with variou...INTRODUCTION: X-linked myotubular myopathy (XLMTM) is a life-threatening congenital disorder characterized by severe respiratory and motor impairment. This disease presents significant therapeutic challenges, with various strategies being explored to address its underlying pathology. Among these approaches, gene replacement therapy has demonstrated substantial functional improvements in clinical trials. However, safety issues emerged across different therapeutic approaches, highlighting the need for further research. AREAS COVERED: This review provides a comprehensive analysis of the data gathered from natural history studies, preclinical models and clinical trials, with a particular focus on gene replacement therapy for XLMTM. The different therapeutic strategies are addressed, including their outcomes and associated safety concerns. EXPERT OPINION: Despite the encouraging potential of gene therapy for XLMTM, the occurrence of safety challenges emphasizes the urgent need for a more comprehensive understanding of the disease's complex phenotype. Enhancing preclinical models to more accurately mimic the full spectrum of disease manifestations will be crucial for optimizing therapeutic strategies and reducing risks in future clinical applications.