肿瘤裂解物颗粒单纯疫苗（TLPO）与负载肿瘤裂解物颗粒的树突状细胞疫苗（TLPLDC）用于预防III/IV期黑色素瘤切除患者复发：一项I/IIa期试验的结果
Tumor lysate particle only vaccine (TLPO) vs. Tumor lysate particle-loaded, dendritic cell vaccine (TLPLDC) to prevent recurrence in resected stage III/IV melanoma patients: Results of a phase I/IIa trial.
作者信息
Van Decar Spencer G, Carpenter Elizabeth L, Adams Alexandra M, Chick Robert C, Clifton Guy T, Stojadinovic Alex, Vreeland Timothy J, Valdera Franklin A, Tiwari Ankur, O'Shea Anne E, McCarthy Patrick M, Hale Diane F, Bohan Phillip M Kemp, Hickerson Annelies T, Cindass Jessica L, Hyngstrom John, Berger Adam C, Jakub James W, Sussman Jeffrey J, Shaheen Montaser, Yu Xianzhong, Wagner Thomas, Faries Mark B, Peoples George E
机构信息
Brooke Army Medical Center, San Antonio, TX, USA.
Brooke Army Medical Center, San Antonio, TX, USA.
出版信息
Cancer Treat Res Commun. 2024;41:100843. doi: 10.1016/j.ctarc.2024.100843. Epub 2024 Sep 11.
BACKGROUND
The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from dendritic cells (DC) loaded ex vivo with autologous tumor lysate (TL). TLPLDC has been shown to decrease recurrence in resected Stage III/IV melanoma patients in a Phase IIb trial. The TL particle only (TLPO) vaccine is produced by loading of yeast cell wall particles with autologous TL and direct injection allowing for in vivo DC loading. We have compared the TLPO and TLPLDC vaccines in an embedded Phase I/IIa trial of a larger Phase IIb trial of the TLPLDC vaccine.
METHODS
Patients rendered clinically disease-free after surgery were randomized 2:1 to receive the TLPO or TLPLDC vaccine and followed for recurrence and death. Patients had scheduled intradermal inoculations at 0, 1, 2, 6, 12, and 18 months after enrollment. Kaplan-Meier and log-rank analysis were used to compare disease-free survival (DFS) and overall survival (OS) in an intention-to-treat (ITT) analysis.
RESULTS
Sixty-three patients were randomized, 43 TLPO and 20 TLPLDC. Patients randomized to the TLPO arm were more likely to be female (37.2% vs. 10.0 %, p = 0.026), but otherwise no significant clinicopathological differences were identified. No differences in related adverse events (AE) were found between treatment arms. At a median follow-up of 20.5 months, the DFS (60.8% vs. 58.7 %, p = 0.714) and OS (94.6% vs. 93.8 %, p = 0.966) were equivalent between the TLPO and TLPLDC groups, respectively. No statistical differences were found in subgroup analyses between vaccine types, which accounted for receipt of immunotherapy and the use of G-CSF pre-blood draw.
CONCLUSIONS
In a randomized, double-blind Phase I/IIa trial, there were no differences in DFS or OS in resected Stage III/IV melanoma patients receiving adjuvant TLPO versus TLPLDC vaccines. Given manufacturing advantages, further efficacy testing of TLPO is warranted in a Phase III trial.
背景
自体肿瘤裂解物负载树突状细胞（TLPLDC）疫苗是由体外负载自体肿瘤裂解物（TL）的树突状细胞（DC）制备而成。在一项IIb期试验中，TLPLDC已被证明可降低III/IV期黑色素瘤切除患者的复发率。单纯TL颗粒（TLPO）疫苗是通过将酵母细胞壁颗粒负载自体TL并直接注射，从而实现体内DC负载来制备的。在TLPLDC疫苗的一项更大规模IIb期试验的嵌入式I/IIa期试验中，我们对TLPO和TLPLDC疫苗进行了比较。
方法
术后临床无疾病的患者按2:1随机分组，分别接受TLPO或TLPLDC疫苗，并随访复发和死亡情况。患者在入组后0、1、2、6、12和18个月安排皮内接种。采用Kaplan-Meier法和对数秩检验在意向性分析（ITT）中比较无病生存期（DFS）和总生存期（OS）。
结果
63例患者被随机分组，43例接受TLPO疫苗，20例接受TLPLDC疫苗。随机分配到TLPO组的患者女性比例更高（37.2%对10.0%，p = 0.026），但在其他方面未发现显著的临床病理差异。治疗组之间未发现相关不良事件（AE）的差异。中位随访20.5个月时，TLPO组和TLPLDC组的DFS分别为60.8%和58.7%（p = 0.714），OS分别为94.6%和93.8%（p = 0.966），两者相当。在按疫苗类型进行的亚组分析中未发现统计学差异，亚组分析考虑了免疫治疗的接受情况和采血前G-CSF的使用情况。
结论
在一项随机、双盲的I/IIa期试验中，接受辅助性TLPO疫苗与TLPLDC疫苗的III/IV期黑色素瘤切除患者的DFS或OS没有差异。鉴于生产优势，有必要在III期试验中对TLPO进行进一步的疗效测试。
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