Circulating immune landscape in melanoma patients undergoing anti-PD1 therapy reveals key immune features according to clinical response to treatment DOI Creative Commons
Eleonora Sosa Cuevas, Stéphane Mouret,

Guillaume Vayssière

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 2, 2024

Introduction Immune checkpoint blockers (ICB) bring unprecedented clinical success, yet many patients endure immune mediated adverse effects and/or fail to respond. Predictive signatures of response ICB and mechanisms efficacy or failure remain understudied. DC subsets, in network with conventional αβ T (T conv ), NK, γδ iNKT cells, harbor pivotal roles tumor control, their involvement remained underexplored. Methods We performed an extensive longitudinal monitoring circulating cells from melanoma treated first-line anti-PD1, before (T0) during treatment. assessed the phenotypic functional features effector cells’ subsets by multi-parametric flow cytometry ProcartaPlex ® dosages. Results revealed differences according treatment modulations patterns treatment, highlighting a strong link between landscape outcome anti-PD1 therapy. Responders exhibited higher frequencies cDC1s, CD8 + γδ2 central memory (CM) stage. Notably, we observed distinct remodeling ICP expression profile, activation status natural cytotoxicity receptor Anti-PD1 modulated DCs’ functionality triggered deep changes orientation γδT cells. Discussion Overall, our work provides new insights into immunological sustaining favorable responses resistance therapy patients. Such exploration participates uncovering mechanism action discovering innovative predictive response, paves way design pertinent combination strategies improve patient benefits future.

Language: Английский

Why do patients with cancer die? DOI
Adrienne Boire, Katy Burke, Thomas R. Cox

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(8), P. 578 - 589

Published: June 19, 2024

Language: Английский

Citations

28
ENGOT-en11/GOG-3053/KEYNOTE-B21: A Randomised, Double-Blind, Phase 3 Study of Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy in Patients With Newly Diagnosed, High-Risk Endometrial Cancer DOI
Toon Van Gorp, David Cibula, Weiguo Lv

et al.

Annals of Oncology, Journal Year: 2024, Volume and Issue: 35(11), P. 968 - 980

Published: Sept. 14, 2024

Language: Английский

Citations

24
Early Effects of Bronchoscopic Cryotherapy in Metastatic Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Single-Center Prospective Study DOI Creative Commons
Gediminas Vasiliauskas,

Evelina Žemaitė,

Erika Skrodenienė

et al.

Diagnostics, Journal Year: 2025, Volume and Issue: 15(2), P. 201 - 201

Published: Jan. 17, 2025

Background/Objectives: Cryotherapy is used for local tissue destruction through rapid freeze–thaw cycles. It induces cancer cell necrosis followed by inflammation in the treated tumor microenvironment, and it stimulates systemic adaptive immunity. Combining cryotherapy with immunotherapy may provide a sustained immune response preventing T exhaustion. Methods: Fifty-five patients metastatic non-small lung who had received no prior treatment were randomized into two groups 1:1 ratio: bronchoscopic group or control group. Patients up to four cycles of pembrolizumab as monotherapy combination platinum-based chemotherapy. Immune-related adverse events (irAEs), complications, size changes, overall rate (ORR), disease (DCR) evaluated. Results: Lung tumors, cryotherapy, demonstrated continuous reduction from baseline (22.4 cm2 vs. 14.4 10.2 cm2, p < 0.001). Similar changes observed pulmonary tumors (19.0 10.0 The median change between was not significant (−42.9% −27.7%, = 0.175). No differences ORR (28.6% 23.1%, 0.461) target lesion decrease (−24.0% −23.4%, 0.296) groups. However, DCR significantly higher (95.2% 73.1%, 0.049). cases serious bleeding during pneumothorax observed. Six (25.0%) eight (26.7%) experienced irAEs. Conclusions: Our study that combined without chemotherapy reduce progressive while maintaining satisfactory safety profile.

Language: Английский

Citations

0
Toxicity Associated with Pembrolizumab Monotherapy in Patients with Gastrointestinal Cancers: A Systematic Review of Clinical Trials DOI Creative Commons

Nikolas Naleid,

Amit Mahipal, Sakti Chakrabarti

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 229 - 229

Published: Jan. 18, 2025

Background/Objectives: Pembrolizumab, an immune checkpoint inhibitor targeting programmed death 1 (PD-1), is a widely employed therapy for various gastrointestinal (GI) cancers. We conducted systematic review of clinical trials investigating pembrolizumab monotherapy in GI cancer patients to assess the spectrum and incidence immune-related adverse events (irAEs) associated with pembrolizumab. Methods: A comprehensive search PubMed/MEDLINE was performed identify patients. Primary endpoints included grade 3 or higher irAEs rate treatment discontinuation due irAEs. Secondary encompassed any-grade irAEs, as well specific Results: Data extraction analysis were on 25 articles. The 3101 median age 62 years (range 53–68), 30.2% being female. Tumor types colorectal (12%), esophagogastric (46%), hepatocellular carcinoma (24%), other tumor (18%). 6.8%. most prevalent hepatitis (3.6%), pneumonitis (0.8%), colitis (0.7%). Death attributed infrequent (0.9%). Conclusions: In cancers treated monotherapy, severe toxicities are infrequent, leading uncommon.

Language: Английский

Citations

0
The evolving treatment landscape for CSCC DOI
David M. Miller

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: Feb. 26, 2025

Language: Английский

Citations

0
Early Prediction of Pembrolizumab-Induced Hypothyroidism Based on the Neutrophil-to-Lymphocyte Ratio DOI Open Access
Yusuke Nakazawa,

Ako Gannichida,

Hirofumi Utsumi

et al.

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Introduction Pembrolizumab, an immune checkpoint inhibitor targeting programmed death-1 (PD-1)/PD-1 ligand (PD-L1), has demonstrated antitumor effects but can cause immune-related adverse events (irAEs) such as hypothyroidism. The neutrophil-to-lymphocyte ratio (NLR) may be linked to pembrolizumab efficacy and irAE risk. This study investigated the relationship between NLR trends hypothyroidism onset, assessing its predictive potential. Methods retrospective analyzed 136 patients with advanced or recurrent cancer treated at Jikei University Hospital, Tokyo, Japan, from February 2017 September 2023. Patients were categorized based on development, their baseline time treatment failure (TTF) compared. before onset also evaluated. further stratified timing (<90 days vs. ≥90 days), parameters prior Results Hypothyroidism occurred in 33 of (24%). group had a significantly lower (P = 0.006) longer TTF 0.006). No significant changes observed 0.626). However, maximum until was early-onset days) 0.016). In contrast, no differences mean minimum NLR. A receiver-operating characteristic (ROC) analysis identified cutoff 4.3 for predicting 0.002, area under curve (AUC) 0.770). Conclusions low associated persistently contribute early onset. These findings suggest that continuous monitoring during aid risk facilitate appropriate management.

Language: Английский

Citations

0
Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III KEYNOTE-716 study DOI
Jason J. Luke, Paolo A. Ascierto, Muhammad Adil Khattak

et al.

European Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 115381 - 115381

Published: March 1, 2025

Language: Английский

Citations

0
Immune-related adverse events among patients with early-stage triple-negative breast cancer treated with pembrolizumab plus chemotherapy: real-world data from the Neo-Real/GBECAM 0123 study DOI Open Access
Matheus de Oliveira Andrade,

Isabella Gonçalves Gutierres,

Monique Celeste Tavares

et al.

The Breast, Journal Year: 2025, Volume and Issue: unknown, P. 104473 - 104473

Published: April 1, 2025

Pembrolizumab combined with neoadjuvant chemotherapy is the standard of care for stage II-III triple-negative breast cancer (TNBC) based on KEYNOTE-522 trial. However, 13 % patients experienced immune-related adverse events (irAEs) grade ≥3 in This study aims to describe patterns irAEs a real-world scenario during treatment pembrolizumab early-stage TNBC. Patients treated plus across ten Brazilian centers were evaluated Neo-Real/GBECAM0123 study. analysis focuses irAE evaluation, including time onset, management, and association between pathological complete response (pCR). A total 368 included. Overall, 31 (n = 114) presented any irAEs. Most (72.8 %) occurred phase while 28.1 happened adjuvant period. The most frequent endocrine (12.8 entire cohort), cutaneous (7.6 gastrointestinal (7.1 %). 50 (13.6 irAEs, predominantly (32 58 (56 needed corticosteroids. Immunotherapy rechallenge was possible 53 cases; permanent discontinuation necessary 16 %. No significant observed clinic-pathologic features nor pCR status. In this analysis, we similar incidence as reported resolution their but some required pembrolizumab. Additionally, there lasting dysfunctions, particularly endocrine, demanding lifelong support. Careful monitoring management these are essential.

Language: Английский

Citations

0
Safety of pembrolizumab as adjuvant therapy in a pooled analysis of phase 3 clinical trials of melanoma, non–small cell lung cancer, and renal cell carcinoma DOI
Jason J. Luke,

Georgina V Long,

Caroline Robert

et al.

European Journal of Cancer, Journal Year: 2024, Volume and Issue: 207, P. 114146 - 114146

Published: May 31, 2024

Language: Английский

Citations

3
Nemvaleukin alfa, a modified interleukin-2 cytokine, as monotherapy and with pembrolizumab in patients with advanced solid tumors (ARTISTRY-1) DOI Creative Commons
Ulka N. Vaishampayan, Jameel Muzaffar, Ira Winer

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(11), P. e010143 - e010143

Published: Nov. 1, 2024

Background Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel, engineered cytokine that selectively binds to the intermediate-affinity interleukin-2 receptor, preferentially activating CD8 + T cells and natural killer cells, with minimal expansion of regulatory thereby mitigating risk toxicities associated high-affinity receptor activation. Clinical outcomes nemvaleukin are unknown. ARTISTRY-1 investigated safety, recommended phase 2 dose (RP2D), antitumor activity in patients advanced solid tumors. Methods This was three-part, open-label, 1/2 study: part A, dose-escalation monotherapy, B, dose-expansion C, combination therapy pembrolizumab. The study conducted at 32 sites 7 countries. Adult tumors were enrolled received intravenous once daily on days 1–5 (21-day cycle) 0.1–10 µg/kg/day (part A), or RP2D B), pembrolizumab C). Primary endpoints selection dose-limiting overall response rate (ORR) safety (parts B Results From July 2016 March 2023, 243 treated (46, 74, 166 parts respectively). maximum tolerated not reached. determined as 6 µg/kg/day. ORR monotherapy 10% (7/68; 95% CI 4 20), seven partial responses (melanoma, n=4; renal cell carcinoma, n=3). Robust expansion, observed following treatment. plus 13% (19/144; 8 5 complete 14 responses; PD-(L)1 inhibitor-approved five inhibitor-unapproved tumor types. Three platinum-resistant ovarian cancer. most common grade 3–4 treatment-related adverse events (TRAEs) respectively, neutropenia (49%, 21%) anemia (10%, 11%); 4% each discontinued due TRAEs. Conclusions well demonstrated promising across heavily pretreated Phase 2/3 studies ongoing. Trial registration number NCT02799095 .

Language: Английский

Citations

3