PO.CL01.16 · 临床研究

真实世界实践中接受tarlatamab治疗的广泛期小细胞肺癌患者的免疫细胞谱变化

Immune cell profile changes in patients treated with tarlatamab for extensive stage small cell lung cancer in real world practice

编号 3931 展板 6 时间 4/20 02:00–05:00 区域 Section 48 主讲 Dhauna Karam Prasad, MD;PhD

分会场 Prognostic Biomarkers 2

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作者与单位 Authors & Affiliations

Dhauna Karam Prasad¹, Andre De Menezes Silva Corraes¹, Malvika Gupta¹, Audrey Ma², Chen Wu¹, Zuoyi Shao¹, Kevin Reagan¹, Rayaan Kamal¹, Ashley Potter¹, Abdullah Al-Ajmi¹, Syeda Mina¹, Sykler J. Taylor¹, Antonious Hazim¹, Anastasios Dimou¹, Kaushal Parikh¹, Mohammed Shanshal¹, Ailsa Luce¹, Anna Schwecke¹, Julian Molina¹, Aaron Mansfield¹, Katherine Smith¹, Lucy Holmes¹, Haidong Dong¹, Yi Lin¹, Konstantinos Leventakos¹

¹Mayo Clinic Cancer Center Minnesota, Rochester, MN,²Columbia University, New York, NY

摘要 Abstract

中文摘要

背景：Tarlatamab是一种靶向Delta样配体（DLL3）/CD3的双特异性T细胞衔接器（TCE），经FDA批准用于一线化学免疫治疗进展后的广泛期小细胞肺癌（ES-SCLC）患者。我们旨在评估在标准治疗（SOC）实践中接受该治疗、无进展生存期（PFS）小于和大于2个月（mo）的患者的免疫细胞谱。方法：本研究纳入在Mayo Clinic Rochester接受tarlatamab治疗并同意进行血液免疫表型分析的患者。免疫表型分析在全血中通过流式细胞术进行，并使用Kaluza进行分析。数据分析使用Microsoft Excel和PRISM进行。结果：本研究纳入18例患者，中位年龄64岁（范围37-79）。我们队列中66%为女性，83%有现在或既往吸烟史，平均40包年（范围26-60）。中位随访2个月，该队列的中位PFS为1.5个月（范围0.33-2.76个月）。61%（13/18）的患者PFS<2个月。39%（5/18）的患者PFS>2个月，其中三例患者达到部分缓解，一例维持疾病稳定，一例出现混合反应。在基线（BL）时，PFS<2个月组与PFS>2个月组之间的T细胞、CD4或CD8细胞计数无差异。PFS<2个月的患者的耗竭型CD8 T细胞高于PFS>2个月组（CD8+PD1+TIGIT+CD57+，PFS<3个月对>3个月，细胞/mL：7.14±4.28，1.58±1.37，p=0.009）。此外，在分析B细胞群时，PFS<2个月组在基线时的B细胞百分比低于PFS>2个月组（6.0±7.5，10.4±14，p=0.02）。在第7天，PFS<2个月组的Treg低于PFS>2个月组（2.88±1.38，4.60±1.47，p=0.02）。同时，在第7天，PFS<2个月组的B细胞较PFS>2个月组增加（<2个月对>2个月：10.0±14，4.37±3.07，p=0.04）。最后，与PFS<2个月组相比，PFS>2个月组在第7天时总单核细胞（mono）、经典单核细胞和免疫抑制性细胞减少（PFS<2个月对>2个月，单核细胞：340±347，253±106，p=0.04。经典单核细胞：305±283，155±109，p=0.02。CD14+HLA-DRneg：105.8±96，12±39，p=0.03）。虽然PFS<2个月组在基线与第7天之间的中间型单核细胞无变化，但PFS>2个月组在治疗后的中间型单核细胞减少（基线对第7天，细胞/mL，中间型单核细胞：32.5±15，17.7±6.2，p=0.03）。结论：在这项研究tarlatamab标准治疗结局的研究中，早期进展与更高水平的耗竭型CD8 T细胞、B细胞和免疫抑制性单核细胞相关。更多患者的分析将在AACR会议上分享。

查看英文原文 English abstract

Background: Tarlatamab, a Delta-like ligand (DLL3)/CD3-targeted bispecific T-cell engager (TCE) is FDA approved in patients (pts) with extensive stage small cell lung cancer (ES-SCLC), after progression on frontline chemoimmunotherapy. We aimed to evaluate the immune cell profile in pts who received this therapy in standard-of-care (SOC) practice with progression free survival (PFS) less than and greater than two months (mo). Methods: Patients who received tarlatamab at Mayo Clinic Rochester and consented to immuno phenotyping of blood are included in the present study. Immune phenotyping was performed on whole blood by flow cytometry and analyzed by Kaluza. Data analysis was performed with Microsoft Excel and PRISM. Results: Eighteen patients with median age 64 (range 37-79) were included in the study. 66% of our cohort were women and 83% had present or past history of smoking, with an average of 40 pack years (range 26-60). With a median follow-up of 2 months, the median PFS for the cohort was 1.5 mo (range 0.33-2.76 months). 61% (13/18) of patients had PFS <2mo. 39% (5/18) had PFS>2mo and of which, three patients had partial response with one maintaining stable disease and one patient with mixed response. At baseline (BL), there were no difference in T cell, CD4 or CD8 cell count between patients in the PFS<2mo and PFS>2mo groups. Patients with PFS<2mo had higher exhausted CD8 T cells compared to those in the PFS>2mo group (CD8+PD1+TIGIT+CD57+, PFS<3mo vs >3mo, cells/mL: 7.14±4.28, 1.58±1.37, p=0.009). Additionally, when analyzing the B-cell population, the PFS<2mo group had lower percentage of B cells compared to the group with PFS>2mo at baseline (6.0±7.5, 10.4±14, p=0.02). At day 7, the group with PFS<2mo had lower Treg compared to the group with PFS>2mo (2.88±1.38, 4.60±1.47, p=0.02). Also, the PFS<2mo group had an increase of B cells compared to the group with PFS>2mo at day 7(<2mo vs >2mo: 10.0±14, 4.37±3.07, p=0.04). Finally, the group with PFS>2mo had decrease in total monocytes (mono), classical mono, and immunosuppressive cells (PFS<2mo vs >2mo, Mono: 340±347, 253±106, p=0.04. Classical mono: 305±283, 155±109, p=0.02. CD14+HLA-DRneg: 105.8±96, 12±39, p=0.03) compared to the group with PFS<2mo by day 7. While no changes were seen between BL and day 7 for intermediate mono in PFS<2mo group, PFS>2mo group had decreased post treatment intermediate monocytes (BL vs day 7, cells/mL, intermed mono: 32.5±15,17.7±6.2, p=0.03). Conclusion: In this study investigating the SOC outcomes of tarlatamab, early progression was associated with higher presence of exhausted CD8 T cells, B cells, and immunosuppressive monocytes. Analysis of additional patients will be shared at AACR meeting.

利益披露 Disclosure

D. Karam Prasad, None.. A. De Menezes Silva Corraes, None.. M. Gupta, None.. A. Ma, None.. C. Wu, None.. Z. Shao, None.. K. Reagan, None.. R. Kamal, None.. A. Potter, None.. A. Al-Ajmi, None.. S. Mina, None.. S. J. Taylor, None.. A. Hazim, None.. A. Dimou, None.. K. Parikh, None.. M. Shanshal, None.. A. Luce, None.. A. Schwecke, None.. J. Molina, None.. A. Mansfield, None.. K. Smith, None.. L. Holmes, None.. H. Dong, None. Y. Lin, Janssen, Sanofi, BMS, Regeneron, Genentech, Tessera, Legend, NexT Therapeutics Other, Advisory Board. Janssen, Kite/Gilead Other, Steering Committee. Janssen, BMS ). NexImmune, Caribou Other, Scientific Advisory Board. Pfizer Other, Data safety monitoring board. K. Leventakos, None.

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