⚡T-Cell Melanoma Trial, Triple-Site Regrowth, and Dupilumab in Pregnancy

Good morning — it's Saturday, Apr. 12, and we're covering a next-generation T cell therapy for melanoma, baricitinib’s triple-site impact in alopecia areata, and more.

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Need To Know

Next-Generation T Cell Therapy for PRAME-Positive Melanoma

A Phase 1 trial published in Nature Medicine found that Immatics’ IMA203, an investigational T cell receptor therapy, demonstrated anti-tumor activity in HLA-A*02+ patients with PRAME-positive refractory solid tumors, including melanoma. PRAME, short for preferentially expressed antigen in melanoma, is a tumor-associated antigen detected in melanoma and other solid tumors.

IMA203 redirects autologous T cells—engineered with a high-affinity T cell receptor—to specifically target PRAME-derived peptides presented on tumor cells by HLA-A*02:01. Unlike chimeric antigen receptor (CAR) T cell therapies, which recognize extracellular proteins, this T cell receptor-based approach enables the targeting of intracellular tumor antigens.

The open-label trial enrolled 40 patients—including 16 with melanoma—who received escalating doses of IMA203. Patients were heavily pretreated, with a median of four prior lines of systemic therapy, and had high baseline tumor burdens.

Overall, 29% of participants achieved a confirmed response, defined as a ≥30% reduction in tumor size or complete disappearance of lesions, verified by follow-up imaging. Among melanoma patients treated at the highest dose levels, the response rate was 50% (5/10), with several cases showing durable disease control beyond 12 months.

The safety profile was favorable: only 5% of patients experienced grade 3 cytokine release syndrome, with no grade 4 or 5 events, and no cases of grade ≥3 neurotoxicity—both of which are potentially life-threatening adverse events known to occur with CAR T cell therapies.

Following these results, Immatics has launched a Phase 3 trial, SUPRAME, in patients with previously treated advanced melanoma. A successful outcome could position IMA203 as a novel option for those with limited response to prior therapies.

Quick Hits

> Baricitinib Drives Triple-Site Regrowth in Severe Alopecia Areata: A new analysis of over 1,200 patients from the BRAVE-AA trials shows that baricitinib promotes significant regrowth of eyebrows and eyelashes in addition to scalp hair in patients with severe alopecia areata. At Week 36, 44% and 46% of patients on baricitinib 4 mg had minimal or no eyebrow and eyelash loss (ClinRO 0/1), respectively, compared to just 13% on placebo. These response rates increased to 56% at both sites by Week 52. Eyebrow and eyelash regrowth were highly concordant: approximately 80% of patients who responded at one site also did so at the other. Among those achieving at least 80% scalp hair coverage (SALT ≤20), 71% also reached ClinRO 0/1 for both eyebrows and eyelashes. Notably, 35% of patients with poor scalp response (SALT >20) still met this target. These findings underscore baricitinib’s ability to address all three major hair-bearing sites in severe alopecia areata through selective JAK1/2 inhibition.

> Dupilumab Shows No Increased Pregnancy Risk in First Large Cohort: A large, propensity-matched cohort study of 293 pregnant women treated with dupilumab for type 2 inflammatory diseases (T2IDs) found no increased risk of adverse pregnancy outcomes. In fact, compared to untreated controls, dupilumab use was associated with a 47% lower risk of any adverse pregnancy outcome (HR 0.53, 95% CI 0.33–0.84). Dupilumab did not increase the risk of individual outcomes—including spontaneous abortion, preterm labor, hypertensive disorders, or gestational diabetes. No elevated risk of postpartum complications was observed. Although the retrospective observational design and reliance on electronic health records limit causal inference, these findings contribute to the existing safety evidence for dupilumab use in pregnancy.

> Largest Ochronosis Series Reveals Signature Dermoscopy Features: A multicenter study conducted by the International Dermoscopy Society analyzed 29 patients with exogenous ochronosis, highlighting key clinical and dermoscopic features. All patients had malar involvement; 41% also had forehead involvement and 35% had nose involvement. Lesion color varied, with grey-brown or brown observed in 66% of cases. Key dermoscopic features distinguish exogenous ochronosis from melasma and acquired dermal macular hyperpigmentation included obliteration of follicular openings (86%), brown amorphous areas (72%), and comma-shaped structures (45%). The latter correlates histologically with “banana bodies.” Other common findings included pigment dots (72%), telangiectasias (52%), an accentuated pigment network (48%), white structureless areas (45%), and rimming of eccrine openings (31%). View key dermoscopic images in the article (paywall restricted).

> Sofwave Improves Acne Scars and Upper Arm Laxity in Twin Trials: A novel ultrasound device (Sofwave) has shown dual efficacy in treating facial acne scars and upper arm laxity, according to twin multicenter open-label trials published in Dermatologic Surgery. In the acne scar trial, mean severity scores decreased from 2.31 to 1.26 (on a 0–3 scale) after at least two treatments, reflecting a 46% reduction in scar severity (P<0.001). Nearly 90% of participants reported satisfaction after three sessions. In the upper arm laxity study, mean severity scores improved from 2.95 to 1.97 (0–4 scale; P<0.0001), and 72% of subjects reported satisfaction after two sessions. Treatments were well tolerated across Fitzpatrick skin types I–VI. Sofwave delivers high-intensity, high-frequency parallel ultrasound beams targeting the mid-dermis at a depth of 1.5 mm. It stimulates collagen and elastin production without relying on skin chromophores, enabling effective dermal remodeling—even in darker skin types.

> Active Education Trial Shows Better Melanoma Detection But Low Follow-Up Limits Conclusions: A randomized trial of 336 non-medical participants evaluated passive versus active education for identifying lesions at risk of melanoma. The passive group received a self-guided booklet on the ABCDE and “ugly duckling” rules, while the active group received the same content explained by a dermatologist. Participants then classified 60 pigmented lesions—nevi and melanomas—using these rules. In both groups, overall detection of “at-risk” lesions improved from 71% at baseline (T0) to approximately 86% immediately post-intervention (T1). Compared to passive education, active intervention led to a modest but significant improvement in detection rates at 30 days (T2) (87% vs. 84%; P = 0.017), along with more frequent correct rule application (80% vs. 76%) at both T1 and T2. However, only 30% of participants completed the final assessment at T2, limiting conclusions about long-term retention.

Derm Picks

Quizzes, cases, and perspectives to sharpen your clinical eye.

🖼️ Image Challenge

• Two chin ulcers that developed after fever (View)

• Annular facial plaques in a 2-month-old (View)

• A painful nodule on the left fifth finger (View)

• Subcutaneous nodules accompanied by joint pain and erythema (View)

🔎 Under the Dermatoscope

• Dermoscopic yellow-white globules in primary balloon cells melanoma (View)

📚 Guides & Reviews

• New systematic review of treatments from solar lentigines (Read)

• A comprehensive and updated algorithm of hidradenitis suppurativa management (Read)

• Update on atopic dermatitis (Read)

• Part 2 of the 2024 updated international guidelines for congenital ichthyoses now published (Read)

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