scholarly journals Pembrolizumab-Induced Lichen Planus on the Scalp of a Patient with Non-Small-Cell Lung Carcinoma

2021 ◽  
pp. 487-491
Author(s):  
Aya Yamashita ◽  
Eijiro Akasaka ◽  
Hajime Nakano ◽  
Daisuke Sawamura

A 67-year-old man with non-small-cell lung carcinoma was referred to our department because of a pruritic rash on his head and upper extremities. Prior to the development of the rash, he had received 4 cycles of combination therapy with pemetrexed, carboplatin, and pembrolizumab, followed by 2 cycles of pembrolizumab monotherapy. On physical examination, violaceous scaly erythema grouped on his scalp and upper extremities. Histologically, the scalp lesions demonstrated irregular acanthosis that formed a characteristic saw-tooth appearance with hypergranulosis and typical lichenoid tissue reaction. These findings suggested that the scalp lesions were lichen planus. Two-week administration of topical corticosteroid dramatically improved the rash. Immunotherapy with pembrolizumab, an anti-PD-1 antibody, can induce T-cell activation that results in various immune-related adverse effects such as lichenoid tissue reaction. However, lichen planus is generally found on the extremities and/or oral mucosa, and unlike in this case, the scalp is rarely affected. Although the exact mechanism underlying predominant scalp involvement is unknown, the present case indicates that anti-PD-1 therapy-induced lichen planus can develop not only on the extremities and oral mucosa but also on the scalp. Interestingly, the lesions were not induced by the combination of chemotherapy and pembrolizumab; rather, they occurred soon after initiation of pembrolizumab monotherapy. In the present case, pembrolizumab-induced T-cell activation which triggered lichenoid tissue reaction may have been suppressed by chemotherapy-induced immunosuppression. Dermatologists should have a thorough knowledge of the cutaneous lesions that manifest as irAEs of anti-PD-1 therapy.

Author(s):  
Li Cheng ◽  
Todd Creasy ◽  
Fernanda Pilataxi ◽  
Lydia Greenlees ◽  
Luis Vence ◽  
...  

AbstractThe rapid development of immune checkpoint blockade (ICB) therapies has revolutionized the cancer treatment landscape and brightened the long-term forecast for many cancer patients. However, the specific genomic and proteomic changes in tumors treated with different ICB treatments have yet to be fully characterized. We treated four non-small-cell lung carcinoma (NSCLC) tumor digests ex vivo with the anti-PD-L1 antibody durvalumab (D) alone or in combination with the anti-CTLA-4 antibody tremelimumab (T) to explore changes in gene and protein expression associated with these ICB therapies. All four tumors showed a robust increase in interferon gamma (IFN-γ) production (100–300% higher than isotype control) in both D- and D + T-treated tumors. Three of the four tumors showed additional increases in IFN-γ production with D + T compared with D (40–70%). A substantial reduction in interleukin 10 (IL-10) was also found in three of the four tumors (reduced to 4–8%) in response to D and D + T. Conventional CD4 + /CD8 + populations and T cell activation markers increased after D and D + T treatment. D and D + T upregulated multiple IPA pathways involving T cell activation. D + T resulted in additional upregulation of Th1/Th2 pathways through a different set of genes, as well as greater reduction in genes involved in epithelial-mesenchymal transition (EMT), angiogenesis, and cancer stemness. Our results demonstrated that D + T augmented the effects of D in the microenvironment of this set of NSCLC tumors. The specific impact of D + T on the regulation of EMT, angiogenesis, and cancer stemness warrants further evaluation in a larger set of tumors.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9046-9046
Author(s):  
Timothy Dudley Clay ◽  
Margarita Majem ◽  
Enriqueta Felip ◽  
Bernard Doger ◽  
Enric Carcereny Costa ◽  
...  

9046 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses in combination than observed with pembrolizumab alone. We hereby report results of the 1st line non-small cell lung carcinoma (NSCLC) part of the phase II trial (NCT03625323). Methods: Patients (pts) with untreated, immunotherapy naïve, advanced NSCLC unselected for PD-L1 expression were recruited into part A. The study used a Simon's 2-stage design (17 pts planned for stage 1 and 19 pts for stage 2), with objective response rate (ORR) by iRECIST as the primary endpoint (EP). Secondary EPs include tolerability, disease control rate (DCR), progression free survival (PFS), overall survival (OS), PK, PD and immunogenicity. Efti is administered as 30 mg subcutaneous injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg intravenous infusion every 3 wks for up to 2 yrs). Imaging was performed every 8 weeks locally and with blinded independent central review (BICR) retrospectively. The study was approved by ethic committees and institutional review boards. Results: In total 36 pts were enrolled. At data cut-off (Jan 2021; median FU of 14 months), the median age was 69 yrs (range 53-84) and 69 % were male. The ECOG PS 0 and 1 was 42% and 58% respectively. Patients had squamous (42%) and non-squamous (58%) NSCLC and 95% presented with metastatic disease. All PD-L1 subgroups (TPS < 1 %, ≥ 1 % to ≤49 %; ≥50 %) were represented with 36% pts having ≥50% TPS. Pts received a median of 7.0 (range 1 – 31) pembrolizumab and 11.5 (range 1-22) efti administrations. Responses as per BICR and local read are shown in the table. ORR (local, iRECIST) by different PD-L1 subgroups was 27% for pts with TPS<1%, 39 % for TPS ≥1 %and 54% for ≥50 % TPS. Median PFS (n=36) was 8.2 months while median OS was not yet reached. The most common (> 20 %) treatment emergent adverse events (AEs) were asthenia (47 %), cough (36 %), decreased appetite (36 %), dyspnea (32 %), pruritus (31 %), fatigue (28 %), diarrhea (25 %), anemia (25 %), constipation (25 %) and back pain (22%). Two patients discontinued treatment due to adverse reactions (Grade 4 immune-mediated hepatitis, Grade 3 AST+ALT increase). Conclusions: Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in 1st line advanced NSCLC patients across all PD-L1 (TPS) levels. Clinical trial information: NCT03625323. [Table: see text]


2015 ◽  
Vol 3 (2) ◽  
pp. 47 ◽  
Author(s):  
Duygu Unalmış ◽  
Zehra Yasar ◽  
Melih Buyuksirin ◽  
Gulru Polat ◽  
Fatma Demirci Ucsular ◽  
...  

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