We report a new case of fixed eruption following the ingestion of Moringa oleifera leaf powder. This case underscores the importance of considering non-medicinal causes, particularly natural products, given their growing popularity.

Background Specific data regarding Progression-Free Survival (PFS) and treatment maintenance estimated by Time To Next Treatment (TTNT) in patients with advanced melanoma responding to first-line treatments are scarce. Objective To evaluate and compare in a real-life setting PFS and overall TTNT in patients with advanced melanoma responding to first-line treatment within three therapeutic subsets: BRAF and MEK inhibitors (group 1), anti-PD1 (group 2) and anti-PD1/Anti-CTLA4 immunotherapies (group 3); and to perform comparative analyses of PFS and TTNT according to response depth (complete or partial response), brain metastases (BM), and per-treatment disease progression. Patients and Methods Patients with unresectable stage III or IV melanoma registered in the French nationwide multicenter Melbase database and responding to first-line immunotherapy or targeted therapy were retrospectively included. Overall and situation-specific PFS and TTNT were assessed and compared within and between therapeutic groups. Results Median PFS was 10.7 months, 84.6 months, and not reached in group 1, 2 and 3 respectively. No obvious difference was observed between PFS and TTNT for patients receiving targeted therapies (TT) and combined anti-PD1/CTLA4 immunotherapy. Conversely, TTNT largely exceeded PFS in patients receiving anti-PD1 alone, with an increasing gap over time. Similar trends were observed in patients with BM and in those experiencing per-treatment disease progression. Conclusion First-line combined anti-PD1/Anti-CTLA4 immunotherapy was associated with the most durable response in patients with advanced melanoma considered as responders, compared with anti-PD1 alone or targeted therapy, independently of BM status. Anti-PD1 monotherapy was frequently maintained beyond disease progression, in contrast to targeted therapy.

Mogamulizumab (MOGA), an anti-CCR4 monoclonal antibody, improves progression-free survival (PFS) and overall survival in Sézary syndrome (SS). Recently, a multicentre retrospective study conducted by the French Cutaneous Lymphoma study group assessed PFS in 52 patients with SS (median age 73 years, 56% female sex, 75% stage IVA1) who discontinued MOGA for reasons other than disease progression (Moga-stop Study). We report data from an extended follow-up of this cohort, along with comparative PFS outcomes from a parallel SS cohort with continuous MOGA treatment until progression.

BACKGROUND:Superpotent topical corticosteroids (STS) are highly effective in bullous pemphigoid (BP), but prolonged use is associated with practical limitations and a risk of relapse. OBJECTIVE:To evaluate whether combining short-term STS with methotrexate (MTX) could maintain efficacy, reduce relapses, and preserve safety compared with prolonged STS alone. METHODS:In this multicentre, randomised, open-label, non-inferiority trial, adults with BP were assigned to receive either STS (clobetasol propionate) for one month plus low-dose MTX as maintenance (MTX + STS arm), or prolonged STS alone (STS arm). The primary endpoint was 9-month overall survival (OS), with a predefined non-inferiority margin of 15%. Secondary outcomes included relapse-free survival (RFS) and severe adverse events (SAE). RESULTS:Among 266 randomised patients (mean age 80.8 years), 9-month OS was 86.5% in the MTX + STS arm and 83.5% in the STS arm (p=0.498; hazard ratio [HR] 0.80, 95% CI 0.40-1.50). The lower limit of the 90% confidence interval for the difference in survival rates (-4.6%) remained within the predefined non-inferiority margin, meeting the primary endpoint. Among the 87.4% of patients who achieved disease control within 28 days, relapse occurred in 31 patients in the MTX + STS arm and 52 in the STS arm, corresponding to a 9-month RFS of 68.4% (95% CI 59.3-78.8) versus 47.4% (95% CI 37.7-59.5), respectively (p=0.042). SAE were more frequent in the MTX + STS arm than in the STS arm (mean number per patient per month 0.40 [95% CI 0.23-0.57] vs 0.19 [95% CI 0.01-0.36], p=0.005). LIMITATIONS:The study was open-label, did not include a validated disease activity score and was conducted in a selected BP population managed under clinical trial conditions. CONCLUSION:Maintenance therapy with low-dose MTX is non-inferior to prolonged STS in terms of survival and is associated with a reduced risk of relapse, at the cost of increased toxicity.

BACKGROUND:The Checkmate 067 randomized controlled trial, published in 2015, demonstrated improved progression-free survival (PFS) and numerically, although not statistically, superior overall survival (OS) for ipilimumab + nivolumab (I + N). OBJECTIVES:The objective of this study was to compare the efficacy and safety of N with I + N as first-line treatment for metastatic melanoma in a real-world setting. METHODS:Patients were prospectively included in the French MelBase cohort from 2013 to 2022. Eligible patients were those in first-line treatment for stage IIIc or IV melanoma, undergoing immunotherapy with N or I + N. The primary endpoint was OS at 36 months. The secondary endpoints included PFS at 36 months, best radiological response, and safety analyses. We conducted a propensity score using the inverse probability of treatment weighting (IPTW) method to overcome the various confounding factors and also a subgroup analysis (brain metastasis, lactate dehydrogenase levels and BRAF mutation status). RESULTS:Patients were treated with N (n = 406) or I + N (n = 416). OS at 36 months was higher in the I + N group at 57.1% [95% confidence interval (CI) 50.7-64.2] than in the N group [46.6% (95% CI 41.6-52.1)]; hazard ratio (HR) 1.4 (95% CI 1.1-1.8). PFS at 36 months was significantly improved in the I + N group (42.3%) compared with the N group (21.9%), with a HR of 1.6 (95% CI 1.4-1.9). The objective response rate (ORR) was similar for the two groups (44%). The overall incidence of side-effects was comparable (82% vs. 84%), and severe toxicity (grade ≥ 3) was more frequent, although not significantly so, in the I + N arm vs. the N arm (41% vs. 29%). CONCLUSIONS:Our results are consistent with those from the Checkmate 067 study, except for the ORR and the incidence of toxicities, which proved to be lower in our analysis.

Cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and sometimes fatal diseases. Patients presenting with advanced-stage CTCL usually exhibit poor long-term survival outcomes. Only very few treatments have improved progression-free survival (PFS) in advanced CTCL, and no treatment has increased overall survival (OS). In 2023, the results of the CUTALLO trial supported the hypothesis that hematopoietic stem-cell transplantation (HSCT) was associated with significantly longer PFS as compared with standard-of-care treatment among advanced-stage patients although HSCT did not significantly affect OS. We provide herein the final OS data pertaining to the same patient population after a longer median follow-up of 38.9 months. Of the 99 patients included in the analysis, 55 (56%) were assigned to the HSCT group, whereas 44 (44%) were allocated to the non-HSCT group. The updated survival analysis reported that 16 of 55 patients (29%) in the HSCT group and 22 of 44 patients (50%) in the non-HSCT group died. The median OS was not reached in the HSCT group and 51.5 months (95% CI, 26.9 to 51.5) in the non-HSCT group (hazard ratio, 0.40 [95% CI, 0.20 to 0.80]). Compared with the standard of care for advanced CTCL, after extended follow-up, allogeneic HSCT was associated with significantly longer OS.

2522 Background: Sézary syndrome (SS) is a rare and aggressive cutaneous T-cell lymphoma, which commonly expresses KIR3DL2, a killer immunoglobulin-like receptor, reported in ≥ 85% of patients. SS is characterized by erythroderma, significant blood involvement, lymphadenopathy and poor prognosis (10-20% 5-year survival). Lacutamab is a first-in-class monoclonal antibody designed to specifically deplete KIR3DL2-expressing cells via antibody-dependent cell-cytotoxicity and phagocytosis. Methods: TELLOMAK is an international, Phase 2 trial with multiple cohorts (NCT03902184). We report here long term follow-up results from Cohort 1, evaluating lacutamab in patients with relapsed/refractory (R/R) SS after at least 2 prior systemic therapies including mogamulizumab. Lacutamab 750 mg is administered until progression or unacceptable toxicity. Primary endpoint was Objective Response Rate (ORR) based on the evaluation of 4 compartments: skin, blood, lymph nodes and viscera according to the International Consensus criteria Olsen 2011. Secondary endpoints included but were not limited to duration of response (DOR), progression free survival (PFS), safety, and quality of life assessments. Results: As of October 17, 2024, recruitment was completed with 63 SS patients enrolled. Median age was 69 years (range: 42-86), the median prior lines of systemic therapies were 5.0 (range: 2-13), 65.1% and 34.9 % patients had stage IVA1 and stage IVA2 at baseline respectively, all patients had blood involvement (B2), 63.5% had confluence of erythema covering ≥ 80% body surface area (T4), 34.9% had lymph node lymphoma involvement (N3). Median follow-up was 25.1 months (95% CI 21.0-29.4). Global confirmed ORR was 42.9% (CI 31.4-55.1) including 6 (9.5%) CRs who are all still in CR; with a median time to response of 2.8 months (range 1-10) and a median duration of response of 25.6 months (CI 11.0, NE). According to each compartment, ORR in skin was 52.4% (CI 40.3-64.2) including 9 (14.3%) CRs, ORR in blood was 50.8% (CI 38.8-62.7) including 21 (33.3) CRs, and ORR in lymph nodes was 28.8% (CI 18.3-42.3) including 9 (17.3) CRs. Median PFS was 8.3 months (CI 5.1-18.7). Grade ≥ 3 related Treatment-Emergent Adverse Events (TEAEs) were observed in 20.6% patients. Serious related TEAEs were observed in 9.5% patients and related TEAEs leading to study drug discontinuation in 6.3% patients. Data from additional key endpoints will be presented. Conclusions: The long term follow-up data from TELLOMAK study in a R/R SS population previously treated with 2 or more prior systemic therapies including mogamulizumab, confirm that lacutamab shows promising clinical activity with ORR 42.9% (95% CI 31.4-55.1) and median duration of response of 25.6 months (11.0, NE) and an overall favourable safety profile. These data support the further development of lacutamab in an effort to bring improved treatments to patients with SS. Clinical trial information: NCT03902184 // EU CT number: 2023-507777-18-00.

9583 Background: Two hedgehog pathway inhibitors (HHIs) have been approved for the treatment of locally advanced basal cell carcinoma (laBCC): vismodegib and sonidegib. Efficacy of both seem similar, even though no head-to-head comparison has been performed. However, adverse events (AEs) in pivotal trials seemed less frequent with a later onset with sonidegib. CARADERM is a French national database created in 2013 to improve the management of rare skin tumors, including laBCC. The objective of our study was to compare the safety profile of HHIs in this real-life cohort. Methods: LaBCC patients from the CARADERM database were reviewed. Patients who started either vismodegib or sonidegib at least one year before analysis were included. Type and grade of AEs were collected when available. Cumulative incidence of the first occurrence of adverse events was estimated, with treatment discontinuation as a competing event. Results: In the total cohort of 452 laBCC patients, 330 met the inclusion criteria: 280 (85%) treated with vismodegib and 50 (15%) with sonidegib. The median follow-up was 22.3 months. Clinical characteristics (including age, gender, performance status, localization and tumor size) were similar for both groups. The cumulative incidence of the first AE was significantly lower with sonidegib (43.5%, 95% confidence interval (95%CI) = 29.0-57.2 at 12 months) than with vismodegib (63.5%, 95%CI = 57.5-68.9 at 12 months, p=0.0014) (Table 1). For vismodegib treated patients, 191 (68%) experienced at least one AE. The most frequent were cramps (n=123, 44%), dysgeusia (n=123, 44%) and alopecia (n=88, 31%). For sonidegib treated patients, 22 (44%) experienced at least one AE. The most frequent were cramps (n=8, 16%), alopecia (n=7, 14%) and dysgeusia (n=6, 12%). Major AEs seemed to be less frequent and to appear later with sonidegib, with a significant difference for cramps (p=0.007) and dysgeusia (p=0.001), but not significant for alopecia (p=0.059). Conclusions: We present here the largest real-life comparison of HHIs in a real-life cohort of laBCC patients. The cumulative incidence of the first AE was significantly lower with sonidegib. Even though the range of AEs was similar with both HHIs, dysgeusia and cramps were less frequent with sonidegib. These data highlight the difference in terms of tolerance of both HHIs, with a later onset and lower frequencies of AEs with sonidegib. However, though both groups were clinically comparable, vismodegib was overrepresented compared to current prescriptions of HHIs, and further analyses are mandatory to confirm these data. Cumulative incidence of first adverse event at 3, 6 and 12 months. 3 months [95CI] 6 months [95CI] 12 months [95CI] Sonidegib 16.3 % [7.5 ; 28.0] 26.8 % [15.2 ; 39.8] 43.5 % [29.0 ; 57.2] Vismodegib 31.6 % [26.2 ; 37.2] 55.5 % [49.5 ; 61.2] 63.5 % [57.5 ; 68.9] 95CI = 95% confidence interval.

Baseline genomic data have not demonstrated significant value for predicting the response duration to MAPK inhibitors (MAPKi) in patients with advanced BRAFV600-mutated melanoma. We used machine learning algorithms and pre-processed genomic data to test whether they could contain useful information to improve the progression-free survival (PFS) prediction. This exploratory analysis compared the predictive performance of a dataset that contained clinical features alone and supplemented with baseline genomic data. In the evaluation set (two cohorts, n = 111), the cross-validated model performance improved when pre-processed genomic data, such as mutation rates, were added to the clinical features. In the validation dataset (two cohorts, n = 73), the best model with genomic data outperformed the best model with clinical features alone. Finally, our best model outperformed with baseline genomic data, increasing the number of patients with a correctly predicted relapse by between +12% and +28%. In our models, baseline genomic data improved the prediction of response duration and could be incorporated into the development of predictive models of MAPKi treatment in melanoma.

Resistance to immune checkpoint inhibitors (ICI) in cancer patients is not fully understood, and predictive biomarkers are lacking. MELANFα (NCT03348891) is an open‐label, prospective, multicenter cohort of 60 patients with advanced melanoma receiving ICI (bitherapy: ipilimumab + nivolumab; monotherapy: pembrolizumab or nivolumab). The primary objective was to evaluate whether changes in plasma TNF between baseline (W0) and week 12 (W12) identified patients with non‐progressive disease at W12. Secondary and exploratory objectives were to assess the association between plasma TNF, tumor response, and changes in circulating T cells. Plasma TNF increased along therapy, but its W12/W0 fold change was not associated with non‐progressive disease at W12. However, plasma TNF levels at W12 were significantly higher in non‐responders than in responders across therapies ( p = .0129). The remodeling of circulating T cell subpopulations was mostly triggered by bitherapy. Increased proportions of circulating central memory and effector memory CD8 T cells after bitherapy were positively and negatively associated with response to treatment, respectively. In this cohort, circulating T cells from responders and non‐responders also displayed distinct molecular characteristics. Indeed, responders showed an increased proportion of CD8 T cells with low enrichment of TNF‐related pathways and high cytotoxic potential, while non‐responders displayed increased proportions of circulating CD8 EM T cells enriched for TNF‐related pathways and directed toward cytokine expression. In conclusion, our study shows that elevated plasma TNF and enriched TNF pathways in T cells are associated with poorer clinical outcomes, reinforcing the notion that TNF may dampen ICI efficacy.

Background: Locally advanced basal cell carcinoma (LaBCC) is a challenging condition. The European Association for Dermato-Oncology (EADO) suggested the classification of laBCC into 5 groups. In this study, we aimed to describe patient characteristics and treatment responses in a large cohort of real-life laBCC patients treated with systemic therapy from a nationwide French database (CARADERM). Methods: LaBCC patients from the CARADERM database were analyzed. Patient demographic data, tumor characteristics, response to treatment and reasons for discontinuation, if applicable, were retrospectively collected. We allocated every patient to the corresponding group according to the EADO classification. Results: The cohort included 452 patients (median age of 77 years and 59 % male sex). LaBCC in the critical zone was the most common group (38 %). Therapeutic response to Hedgehog inhibitors after 10 months of follow-up was evaluated in 353 patients. Complete (CR) and partial response were 39 % and 49 %. Patients with common laBCC achieved CR more frequently (47 %) than patients with very advanced BCC (29 %). Among the 55 patients who achieved CR and stopped treatment, 25 relapsed. The cumulative incidence of relapse at 18 months was 64.2 % (95 % confidence interval (95CI) = 44.6;78.4). The treatment discontinuation rate at 2 years was 88.1 % (95CI = 83.8;91.3). Sonidegib appeared more tolerable. Conclusion: In this largest ever real-life laBCC cohort, tumors were more frequently involving critical areas. The response to treatment was not significantly different between clinical groups, although patients with very advanced BCC had a lower CR rate. The overall efficacy was comparable to that of pivotal trials.

The link between palliative care and oncology must continue to develop, taking into account advances in treatment.Immune checkpoint inhibition (ICI) for metastatic melanoma is associated with different types of response, making it difficult to assess the benefits to the patient. Some clinical trials suggest a survival advantage of ICI even in the absence of an objective radiographic response. The aim of this study is to assess the impact of continuing ICI after progression of the disease on the overall survival (OS) in a cohort of final-line metastatic melanoma patients. Clinical data from 120 patients with metastatic melanoma were collected via Melbase, a French multicentric biobank, prospectively enrolling unresectable melanoma. Two groups were defined: patients continuing final-line ICI at progression (treated) and patients stopping ICI at progression (controls). The primary end-point is the OS from progression. Propensity score weighting was used to correct for indication bias. From the 120 patients, 72 (60%) continued ICI. Median OS from progression was 4.2 months [95% confidence interval (CI) 2.6-6.27] in the treated group and median OS was 1.3 months (95% CI 0.95-1.74) in the control group (P < 0.0001). The calculated hazard ratio was 0.20 (0.13-0.33). Continued ICI was discovered to have an association with a higher rate of hospitalization at the end of life; more treatments received in the last 15 days of life and less utilization of specialist palliative care. This study discovered that patients with metastatic melanoma show a significant decrease in the instantaneous probability of mortality when they continue with finale-line ICI after progression.