Cutaneous Immune-Related Adverse Event Risk High With TVEC Plus ICIs

These study results indicate that the addition of TVEC to ICI therapy increased risk for cirAEs and mortality.

The addition of talimogene laherparepvec (TVEC) to immune checkpoint inhibitors (ICIs) for the treatment of cutaneous malignancy was associated with a 2-fold increase in cutaneous immune-related adverse events (cirAEs) compared with ICIs alone. These study findings were published in Journal of the American Academy of Dermatology.

Researchers retrospectively reviewed patient data collected from Massachusetts General Brigham health care system. Patients (N=892) with cutaneous malignancy who received ICIs with or without TVEC between 2014 and 2022 were evaluated for cirAEs.

The study participants received either ICIs with TVEC (n=93) or ICIs alone (n=799). The dual therapy and monotherapy groups had a median age of 68.2 (IQR, 61.7-77.4) and 65.1 (IQR, 56.4-74.3) years at ICI initiation (P =.002), respectively. A total of 52.7% and 61.6% of the participants were men, 96.8% and 97.4% were White, 83.9% and 95.7% had melanoma (P <.001), and 61.3% and 71.8% received anti-programmed cell death 1 (PD-1) therapy (P =.016) in the dual therapy and monotherapy groups, respectively.

The rates of cirAEs were 38.7% in TVEC recipients and 32.3% among ICI monotherapy recipients. The grade of cirAE severity tended to be lower among the TVEC recipients compared with the ICI monotherapy recipients (median, 1 vs 1.5; P =.081), respectively. The time to cirAEs was delayed among the TVEC recipients (median, 124 days) compared with those in the ICI alone group (median, 55 days; P =.014).

More individualized education and management can improve decision-making and quality of life for patients and caregivers.

Among those in the TVEC group, 77.4% started ICI before TVEC, 12.9% started ICI after TVEC termination, 6.5% started ICI during TVEC therapy, and 3.2% started both on the same day.

When stratifying patients on the basis of ICI initiation timing, the group who started ICI on the same day as TVEC had the shortest time to cirAE (median, 43 days), followed by ICI before TVEC (median, 112 days), ICI during TVEC (median, 130 days), and ICI after TVEC (median, 231 days).

In the multivariate analysis, risk for cirAE was associated with Charlson comorbidity index (CCI) of 0 compared with 5 or more (hazard ratio [HR], 4.35; 95% CI, 1.43-13.2; P =.009) and receipt of TVEC (HR, 2.03; 95% CI, 1.22-3.36; P =.006).

Overall, the 2 groups had a similar mortality rate (47.3% vs 42.2%; P =.403) for TVEC and ICI alone, respectively. In the multivariate model, mortality was associated with TVEC (HR, 2.20; 95% CI, 1.60-3.05; P <.001), other skin malignancy compared with melanoma (HR, 2.09; 95% CI, 1.43-3.06; P <.001), and age at ICI initiation (HR, 1.03; 95% CI, 1.02-1.04; P <.001). Risk for mortality was decreased among patients with a CCI of 1 to 2 (HR, 0.41; 95% CI, 0.29-0.58; P <.001) or 3 to 4 (HR, 0.51; 95% CI, 0.35-0.74; P <.001) compared with 5 or more and among men (HR, 0.80; 95% CI, 0.65-0.98; P =.034).

The study authors conclude, “Our study highlights the importance of closer monitoring strategies and appropriate counseling for those who are considering or receiving ICI and TVEC. More individualized education and management can improve decision-making and quality of life for patients and caregivers.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Dermatology Advisor


Leung BW, Wan G, Nguyen N, et al. Increased risk of cutaneous immune-related adverse events in patients treated with talimogene laherparepvec and immune checkpoint inhibitors: a multi-hospital cohort study. J Am Acad Dermatol. 2023;S0190-9622(23)00268-2. doi:10.1016/j.jaad.2023.02.017