Safety of adoptive therapy with tumor-infiltrating lymphocytes and high-dose recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis.
S Martín-Lluesma, U Dafni, K Vervita, D Karlis, G Dimopoulou, Z Tsourti, G Villacampa, V Galvao, J Lostes, E Muñoz-Couselo, M Rotxés, X Villalobos, S Muñoz, J B A G Haanen, I M Svane, J M Piulats, J Martin-Liberal, A Gros, G Coukos, E Garralda
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引用次数: 0
Abstract
Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has consistently shown efficacy in advanced melanoma. Its combination with non-myeloablative but lymphodepleting (NMA-LD) chemotherapy and high-dose interleukin-2 (HD-IL-2) inevitably lead to severe treatment-related adverse events. The systematic recording of the observed toxicities, which is the aim of the present meta-analysis, will further enhance the implementation and management of this treatment schema.
Methods: A comprehensive search was conducted in PubMed up to 29 February 2024. In this meta-analysis we focused on studies of treatment-refractory advanced cutaneous melanoma with TILs administered in combination with NMA-LD chemotherapy and HD-IL-2 (≥600,000 IU/kg). Our primary endpoint was severe adverse events (AEs) of grade 3 or higher. The safety data was consistently coded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Findings are synthesized using tables, while pooled estimates for groups of AEs of particular interest are derived from random effect models.
Results: A total of 12 HD-IL-2 studies, of 670 patients, with available toxicity information were included in this meta-analysis. Blood toxicities were identified as the most common AEs. In the frame of the formal meta-analysis the pooled estimate of the probability of febrile neutropenia was 60% (95%CI: 36%-83%). The total pooled estimate for the probability of severe "immunologic reaction" events, was 4% (95% CI: 1%- 6%), while the respective probability for experiencing a severe AE in MedDRA SOC category 'Infections and infestations' was 8% (95% CI: 4%- 11%). In addition, in total, 9 fatal (grade 5) AEs have been reported, mostly stated as not attributed to the treatment or attributed to NMA/HD-IL-2.
Conclusions: TIL-ACT, a new approved and promising therapy for melanoma patients, presents a distinctive toxicity profile that is currently manageable with supportive care methods, with reported toxicities mainly arising from NMA-LD chemotherapy and HD-IL-2, and a low risk of severe immunologic reaction events. Continued systematic recording and publication of adverse events, even the rare ones, and its relation to treatment components, are essential to move the field forward.
期刊介绍：
Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine.
The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings.
Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.
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