• 截止2017年1月31日,9例黑色素瘤患者接受TIL过继性细胞治疗(二期临床实验);
  • 超过3例出现低磷酸盐血症(3-4级),无>3级神经毒性,目前未出现因细胞免疫治疗引起的SAE致死或被迫停药;
  • ORR为33%(CR = 11%,PR = 22%,SD = 22%,PD = 33%,NE = 11%);
  • 平均最佳反应时间为3个月,输入细胞14天后,所有患者体内TIL依然保留;
  • 对于晚期转移性且PD1抗体耐受的黑色素瘤患者,TIL细胞治疗是一种可接受的安全治疗方案。

Efficacy of single administration of tumor-infiltrating lymphocytes (TIL) in heavily pretreated patients with metastatic melanoma following checkpoint therapy



Abstract & Authors:展开

Background: Adoptive cell therapy with TIL involves collection of autologous lymphocytes from the tumor via surgical resection, ex vivo expansion of TIL, lymphodepletion of the patient prior to infusion of TIL using Fludarabine and Cyclophosphamide, followed by infusion of TIL. Up to 6 doses of IL-2 (600,000 IU/kg) is administered to support multiplication of TIL and engraftment. Here, we present the preliminary results from an ongoing, multi-site Phase 2 study of TIL for advanced metastatic melanoma.
Methods: Patients with advanced metastatic melanoma who have failed at least one prior systemic therapy were enrolled. Primary objective of the study was to characterize safety profile of LN-144. At baseline, patients had a median age of 56 (41-72) years; 44% were ≥ 60 years old. Median sum of tumor diameters for the target lesions was 10.4 cm, and median of 3 prior therapies. All enlisted patients had prior anti-PD1 as well as anti-CTLA4 and 67% had received ≥ 3 prior therapies. Responses were assessed by RECIST 1.1. TIL products were centrally manufactured. No complications arose from shipment of tumors or TIL.
Results: Results are presented through 31 Jan 2017 for the first 9 infused patients evaluable by two assessments. Eight of 9 patients received all 6 doses of IL-2 per protocol. The most common (≥3 patients) non-hematologic grade 3-4 TEAE was hypophosphatemia. No neurotoxicity of grade ≥ 3 was reported. There were no deaths or discontinuations due to SAEs related to study treatment. ORR was 33% (CR = 11%, PR = 22%, SD = 22%, PD = 33%, NE = 11%). Mean time to best response was 3.0 months and median duration of follow up was 3.6 months (1.1+, 12.1). Responses were observed in patients with tumors carrying wild type or BRAF mutations. All patients demonstrated persistence of TIL on day 14 post-infusion.
Conclusions: Cell therapy with TIL is an effective treatment with acceptable safety profile for advanced metastatic melanoma patients who are refractory to anti-PD1. TIL products can be centrally manufactured for broad clinical application. This study will be expanded to enroll patients with a shorter manufacturing process as well as offering retreatment for study patients.

All Authors:
Amod Sarnaik