肿瘤裂解物颗粒疫苗（TLPO）与肿瘤裂解物颗粒负载树突状细胞疫苗（TLPLDC）用于预防切除的 III/IV 期黑色素瘤患者复发：I/IIa 期试验结果。

Q3 Medicine

Cancer treatment and research communications Pub Date : 2024-01-01 DOI:10.1016/j.ctarc.2024.100843

Spencer G. Van Decar , Elizabeth L. Carpenter , Alexandra M. Adams , Robert C. Chick , Guy T. Clifton , Alex Stojadinovic , Timothy J. Vreeland , Franklin A. Valdera , Ankur Tiwari , Anne E. O'Shea , Patrick M. McCarthy , Diane F. Hale , Phillip M Kemp Bohan , Annelies T. Hickerson , Jessica L. Cindass , John Hyngstrom , Adam C. Berger , James W. Jakub , Jeffrey J. Sussman , Montaser Shaheen , George E. Peoples

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引用次数: 0

摘要

背景：自体肿瘤裂解物颗粒负载树突状细胞（TLPLDC）疫苗由体内外负载自体肿瘤裂解物（TL）的树突状细胞（DC）制成。在一项 IIb 期试验中，TLPLDC 被证明能降低切除的 III/IV 期黑色素瘤患者的复发率。纯TL颗粒（TLPO）疫苗是通过在酵母细胞壁颗粒中加入自体TL，然后直接注射使体内DC加入而制成的。我们在 TLPLDC 疫苗大型 IIb 期试验的嵌入式 I/IIa 期试验中比较了 TLPO 和 TLPLDC 疫苗：方法：手术后无临床症状的患者按 2:1 随机分配接受 TLPO 或 TLPLDC 疫苗，并随访复发和死亡情况。患者按计划在入组后的 0、1、2、6、12 和 18 个月进行皮内接种。在意向治疗（ITT）分析中，采用卡普兰-梅耶尔分析和对数秩分析比较无病生存期（DFS）和总生存期（OS）：63名患者接受了随机治疗，其中43人接受了TLPO治疗，20人接受了TLPLDC治疗。随机进入TLPO治疗组的患者中女性比例更高（37.2% vs. 10.0%，p = 0.026），但在其他方面没有发现明显的临床病理学差异。治疗组之间在相关不良事件（AE）方面没有发现差异。在中位随访 20.5 个月时，TLPO 组和 TLPLDC 组的 DFS（60.8% 对 58.7%，p = 0.714）和 OS（94.6% 对 93.8%，p = 0.966）分别相当。疫苗类型之间的亚组分析未发现统计学差异，其中考虑了接受免疫疗法和抽血前使用G-CSF的情况：结论：在一项随机双盲 I/IIa 期试验中，接受 TLPO 与 TLPLDC 疫苗辅助治疗的 III/IV 期黑色素瘤切除患者的 DFS 或 OS 没有差异。鉴于TLPO在生产方面的优势，有必要在III期试验中对其进行进一步的疗效测试。

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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

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.

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来源期刊

Cancer treatment and research communications Medicine-Oncology

CiteScore

4.30

自引率

0.00%

发文量

148

审稿时长

56 days

期刊介绍： Cancer Treatment and Research Communications is an international peer-reviewed publication dedicated to providing comprehensive basic, translational, and clinical oncology research. The journal is devoted to articles on detection, diagnosis, prevention, policy, and treatment of cancer and provides a global forum for the nurturing and development of future generations of oncology scientists. Cancer Treatment and Research Communications publishes comprehensive reviews and original studies describing various aspects of basic through clinical research of all tumor types. The journal also accepts clinical studies in oncology, with an emphasis on prospective early phase clinical trials. Specific areas of interest include basic, translational, and clinical research and mechanistic approaches; cancer biology; molecular carcinogenesis; genetics and genomics; stem cell and developmental biology; immunology; molecular and cellular oncology; systems biology; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; cancer policy; and integration of various approaches. Our mission is to be the premier source of relevant information through promoting excellence in research and facilitating the timely translation of that science to health care and clinical practice.