(LSM P1) Factors Predicting Toxicity and Response Following Isolated Limb Infusion for Melanoma: An International Multi-center Analysis

Introduction: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to patients with locally advanced or in-transit melanoma confined to a limb. The aim of this international multi-center study was to identify predictive factors for toxicity and response after ILI for Stage IIIB/C limb melanoma.

Methods: Data from patients who underwent a first ILI between 1992-2018 were collected at five Australian and four US tertiary referral centers. Primary outcome measures were toxicity and response.

Results: After ILI, 487 (71%) of 687 patients experienced grade I/II limb toxicity, 165 (24%) grade II, and 27 (4%) grade IV toxicity (missing n=8; 1%). No patient had grade V toxicity (necessitating amputation). Predictive factors for more severe limb toxicity were female gender, lower limb procedures, higher melphalan dose and increased drug circulation and ischemia times. An overall response was observed in 441 patients (64.1%), of whom 199 (28.9%) had a complete response (CR). Patients with a CR had a lower burden of disease, earlier stage of disease (stage IIIB vs. IIIC) and a lower Breslow thickness of the primary melanoma. In addition, an overall response was associated with female gender, lower limb ILI, lower actinomycin-D doses and a delayed serum creatine phosphokinase peak.

Conclusion: This international multi-center study shows that ILI is safe and effective to treat locally advanced limb melanoma. Knowledge of the predictive factors for toxicity and response will improve patient selection and allow optimization of intra-operative factors to increase response rates, while keeping toxicity low.