Background: Standard combination ipilimumab/nivolumab (I/N) is given as 4 induction doses for advanced stage melanoma followed by nivolumab single-agent maintenance therapy. While many patients receive less than 4 doses due to immune-related toxicities, it is unclear if fewer doses of I/N may still provide long term clinical benefit. Our aim is to determine if response assessment after 1 or 2 doses of I/N can predict long-term survival and assess if fewer doses of I/N can lead to similar survival outcomes.
Methods: We performed a retrospective analysis on a cohort of patients with advanced melanoma who w0ere treated with standard I/N. Cox regression of progression-free survival (PFS) and overall survival (OS) models were performed to assess the relationship between response after 1 or 2 doses of I/N and risk of progression and/or death. Clinical benefit response (CBR) was assessed, defined as SD (stable disease) + PR (partial response) + CR (complete response) by imaging. Among patients who achieved a CBR after 1 or 2 doses of I/N, a multivariable Cox regression of survival was used to compare 1 or 2 vs 3 or 4 doses of I/N adjusted by known prognostic variables in advanced melanoma.
Results: 199 patients were evaluated. Patients with CBR after 1 dose of I/N had improved PFS (HR: 0.16, 95% CI 0.08-0.33; p<0.001) and OS (HR: 0.12, 0.05-0.32; p<0.001) compared to progressive disease (PD). Patients with CBR (vs PD) after 2 doses of I/N also had improved PFS (HR: 0.09, 0.05-0.16; p<0.001) and OS (HR: 0.07, 0.03-0.14; p<0.001). There was no survival risk difference comparing 1 or 2 vs 3 or 4 doses of I/N for PFS (HR: 0.95, 0.37-2.48; p=0.921) and OS (HR: 1.04, 0.22-4.78; p=0.965).
Conclusions: Early interval imaging with response during induction with I/N may be predictive of long-term survival in advanced stage melanoma. CBR after 1 or 2 doses of I/N is associated with favorable survival outcomes, even in the setting of fewer I/N doses received. Further studies are warranted to evaluate if electively administering fewer combination I/N doses despite tolerance in select patients may balance the benefits of therapy while decreasing toxicities.
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http://dx.doi.org/10.3389/fimmu.2022.860421 | DOI Listing |
Introduction: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.
View Article and Find Full Text PDFJ Sex Med
January 2025
Andrology and Gender Endocrinology Unit, Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, 50134, Italy.
Background: In males, adenosine (ADO) is known to relax penile smooth muscles, although its role in the vagina is not yet fully elucidated.
Aim: This study investigated the effect of ADO on vagina smooth muscle activity, using a validated female Sprague-Dawley rat model.
Methods: Contractility studies, using noradrenaline-precontracted vaginal strips, tested the effects of ADORA1/3 antagonists and ADORA2A/2B antagonists and agonists.
Int J Drug Policy
December 2024
Consortium on Substance Use and Addiction, Pennsylvania State University, USA; Department of Human Development and Family Studies, Pennsylvania State University, USA.
Virol J
November 2024
Faculty of Pharmacy, Catholic University "Our Lady of Good Counsel", Rr. Dritan Hoxha, 123, Tirana, Albania.
Although not as lethal as variola virus (VARV), the cause of smallpox, monkeypox virus (MPXV) represents a threat to public health, with important infection rates and mortality in several African countries and signs of spreading worldwide. MPXV may establish new reservoirs in non-endemic countries and can be considered a possible biological weapon. Human-to-human MPXV transmission is increasing with a growing susceptibility, coincident with the declining herd immunity against smallpox.
View Article and Find Full Text PDFPestic Biochem Physiol
November 2024
Department of Food Science & Nutrition, College of Food and Agricultural Sciences, King Saud University, 11 P. O. Box 2460, Riyad, 11451, Saudi Arabia.
Abamectin (ABN) is an agricultural insecticide that is reported to damage various body organs including the heart. Velutin (VLN) is a plant-derived flavonoid that exhibits a wide range of medicinal properties. This study was planned to investigate the medicinal value of VLN against ABN induced cardiotoxicity in rats.
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