Effect of the Number of Vaccine Doses Before Starting Anti-CD20 Therapy on Seroprotection Rates Against Hepatitis B Virus in People With MS.

Background And Objectives: Hepatitis B vaccination (HBV) requires 6 months to complete and is recommended for patients with multiple sclerosis (PWMS), particularly those who are candidates for anti-CD20 therapy. However, limited data exist on HBV immunogenicity in PWMS receiving disease-modifying therapies (DMTs) and the impact of starting anti-CD20 therapy during immunization. We aimed to evaluate HBV immunogenicity in PWMS starting anti-CD20 therapy during vaccination, focusing on the number of doses received before anti-CD20 initiation.

Treatment sequence with tebentafusp and immune checkpoint inhibitors in patients with metastatic uveal melanoma and metastatic GNA11/GNAQ mutant melanocytic tumors.

Background: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study.

Dose Individualization for Phase I Cancer Trials With Broadened Eligibility.

Broadening eligibility criteria in cancer trials has been advocated to represent the intended patient population more accurately. The advantages are clear in terms of generalizability and recruitment, however there are some important considerations in terms of design for efficiency and patient safety. While toxicity may be expected to be homogeneous across these subpopulations, designs should be able to recommend safe and precise doses if subpopulations with different toxicity profiles exist.

Meeting Report From the 2023 Cure Ocular Melanoma (CURE OM) Global Science Meeting, Philadelphia, PA, November 2023.

The 2023 Cure Ocular Melanoma (CURE OM) Global Science Meeting was held in Philadelphia on November 6, 2023. There is increased awareness and dedicated research in uveal melanoma (UM), but unmet needs remain in the prevention, detection, and treatment of UM. The purpose of this meeting was to provide an international forum for the exchange of research ideas, to allow for discussion of basic science as well as clinical research on UM, and to gather input about advocacy and patient needs.

Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma.

Background: Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.

Patients And Methods: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+.

Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients.

Vaccine Safety and Immunogenicity in Patients With Multiple Sclerosis Treated With Natalizumab.

Importance: Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay.

Objective: To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment.

Design, Setting, And Participants: This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022.

Prediction of disease activity and treatment failure in relapsing-remitting MS patients initiating daily oral DMTs.

Background: Limited data exist regarding treatment response prediction to oral disease-modifying therapies (DMTs) in multiple sclerosis (MS).

Objectives: We assessed the capacity of available scoring systems to anticipate disease activity parameters in naïve relapsing-remitting MS (RRMS) patients initiating daily oral DMTs, hypothesizing that they exhibit different predictive potentials.

Methods: We conducted a retrospective study and applied the Rio Score (RS), modified Rio Score (mRS), and MAGNIMS Score 12 months after DMT initiation.

Updates in the Management of Uveal Melanoma.

Uveal melanoma (UM), arising from intraocular melanocytes, poses a complex clinical challenge with a substantial risk of distant metastasis, often to the liver. Molecular profiling, encompassing genetic, cytogenetic, gene expression, and immunological subsets, plays a pivotal role in determining prognoses. The evolving landscape includes promising systemic treatments, such as tebentafusp, a novel immune-modulating bispecific fusion protein, and targeted therapies.

Outcome Measurement Instruments Used to Evaluate Dermatologic Adverse Events in Cancer Trials: A Systematic Review.

Importance: Assessment of type, severity, and impact of dermatologic adverse events (DAEs) necessitates well-developed and validated clinician-reported outcome measures (ClinROMs) and patient-reported outcome measures (PROMs) that evaluate concepts specific to mucocutaneous toxic effects and that allow appropriate interpretation and comparison of DAEs across trials.

Objective: To evaluate heterogeneity and quality of ClinROMs and PROMs used to assess DAEs from systemic cancer therapy.

Evidence Review: Two systematic reviews were conducted by searching PubMed and Embase databases from inception through March 7, 2023, and April 12, 2023.

Cutaneous type IV hypersensitivity reaction following tebentafusp treatment for uveal melanoma.

Tebentafusp is a bispecific protein that recently underwent FDA approval for the treatment of metastatic uveal melanoma that functions by redirecting cytotoxic T cells to glycoprotein-100, a protein highly expressed in melanoma. Although clinical trials have demonstrated that rashes are common in the first few days of treatment, little is known about skin reactions that develop later in the treatment course. Herein, we describe a type IV hypersensitivity reaction and vitiligo-like depigmentation that developed six weeks into treatment and discuss the possible mechanisms underlying these reactions.

A phase 2, multicenter, open-label study of anti-LAG-3 ieramilimab in combination with anti-PD-1 spartalizumab in patients with advanced solid malignancies.

Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated).

An Optimal Integral Controller for Adaptive Optics Systems.

Integral controllers are commonly employed in astronomical adaptive optics. This work presents a novel tuning procedure for integral controllers in adaptive optics systems which relies on information about the measured disturbances. This tuning procedure consists of two main steps.

Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma.

Background: Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.

Methods: We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level.

Proceedings from the Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA).

Mucosal melanoma remains a rare cancer with high mortality and a paucity of therapeutic options. This is due in significant part to its low incidence leading to limited patient access to expert care and downstream clinical/basic science data for research interrogation. Clinical challenges such as delayed and at times inaccurate diagnoses, and lack of consensus tumor staging have added to the suboptimal outcomes for these patients.

Frequency of diminished ovarian reserve in women with multiple sclerosis in Chile: An exploratory study.

Introduction: Multiple Sclerosis (MS) is a chronic disease affecting around 2.8 million people worldwide. Two-thirds are women, and the mean age at diagnosis is about 30 years old.

Antimicrobial, Antioxidant, and Anti-Inflammatory Properties of Monofloral Honeys from Chile.

Honey is a mixture of compounds produced by bees that has been appreciated by humanity since the creation of the oldest civilizations. It has multiple uses and can be a highly nutritional and healing substance. It has been used in traditional medicine as a natural alternative for the treatment of diverse clinical conditions.

A single-dose strategy for immunization with live attenuated vaccines is an effective option before treatment initiation in multiple sclerosis patients.

Background: Mumps-Measles-Rubella (MMR) and Varicella zoster vaccines (VAR) are live attenuated vaccines, usually administered in a two-dose scheme at least 4 weeks apart. However, single-dose immunization schemes may also be effective and can reduce delays in immunosuppressive treatment initiation in patients with multiple sclerosis (pwMS) who need to be immunized.

Objectives: To evaluate the immunogenicity of a single-dose attempt (SDA) versus the standard immunization scheme (SIS) with VAR and/or MMR in pwMS.

A phase Ib trial of combined PKC and MEK inhibition with sotrastaurin and binimetinib in patients with metastatic uveal melanoma.

Background: Uveal melanoma is a disease characterized by constitutive activation of the G alpha pathway and downstream signaling of protein kinase C (PKC) and the mitogen-activated protein kinase (MAPK) pathway. While limited clinical activity has been observed in patients with metastatic disease with inhibition of PKC or MEK alone, preclinical data has demonstrated synergistic antitumor effects with concurrent inhibition of PKC and MEK.

Method: We conducted a phase Ib study of the PKC inhibitor sotrastaurin in combination with the MEK inhibitor binimetinib in patients with metastatic uveal melanoma using a Bayesian logistic regression model guided by the escalation with overdose control principle (NCT01801358).

Kinetics of RTK activation determine ERK reactivation and resistance to dual BRAF/MEK inhibition in melanoma.

The combination of BRAF and MEK inhibitors (BRAFi/MEKi) has shown promising response rates in treating BRAF-mutant melanoma by inhibiting ERK activation. However, treatment efficacy is limited by the emergence of drug-tolerant persister cells (persisters). Here, we show that the magnitude and duration of receptor tyrosine kinase (RTK) activation determine ERK reactivation and persister development.