Intralesional anti-PD1 treatment in patients with metastatic melanoma: The pilot studyстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 23 сентября 2021 г.
Аннотация:Background: Systemic anti-PD1 treatment is major advantage for metastatic melanoma patients over the last five years. Nevertheless up to the moment there are no solid predictive factors discovered. On the other hand immune related adverse events develop quite frequent and sometimes could be dangerous. Methods: Patient with advanced cutaneous melanoma with known BRAF status and at least one superficial lesion (suitable for injection) are eligible. One of two commercially available anti-PD1 drugs (nivolumab or pembrolizumab) is administered intralesionaly to patients every 2 weeks with total daily dose not more than 50 mg (5 ml) using a scale-base approach depending on lesions size. Clinical and immunological outcomes assessed every 12 weeks. For assessing lymphoid infiltrate tumor biopsy performed before treatment and on week 12. To detect a systemic objective response rate of 50% with sensitivity of 80% and error type alfa 5% at least 25 patients to be included. Interim analysis was preplanned when 3 (25%) of events occurred. Results: Among 7 pts OR was detected in 4 (54.7%), PD in 3 (42.9%). Bystander effect was seen in 2 of 4 patients (50%). Among 3 non-responders 2 failed to salvage systemic anti-PD1 treatment and one is now on anti-CTLA4. The most common adverse event was injection site pain, which was self-limiting. Baseline immune phenotype of tumor infiltrating lymphocytes (TILs) was available for 5 of 7 pts included. Baseline percent of TILs, CD3+CD8+ and CD8+CD279+ was higher in responders vs non-responders (3.6±4.08% vs 0.8±0, NS, 75.1±20.6% vs 54.8±1.13, NS; 36.75±18.7% vs 42.8±13.1, NS respectively ). Baseline difference in CD11b+CD28- between responders (7.06±7.768) and non-responders (25.0 ±0.00) was statistically significant. Conclusions: these results demonstrates feasibility, tolerability and potential clinical efficacy of intralesional anti-PD1 in melanoma patients. Further study are needed to determine if unsuccessful intralesional administration could predict failure to systemic treatment as well as TILs phenotype could predict intralesional or systemic anti-PD1 clincal benefit Clinical trial information: MEL004IL.