The efficacy of ICIs rechallenge in advanced small cell lung cancer after progression from ICIs plus chemotherapy: A real-world study

IF 4.7 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-04-16 Epub Date: 2025-03-05 DOI:10.1016/j.intimp.2025.114372

Fen Liu , Guisen Yin , Ye Tao , Yong Pan

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Abstract

Background

Rechallenging immune checkpoint inhibitors(ICIs) after resistance to initial ICIs plus chemotherapy(chemo-ICIs) remains uncertain in advanced small cell lung cancer(SCLC).

Method

The study retrospectively enrolled advanced SCLC patients who received ICIs after developing resistance to chemo-ICIs during hospitalization at Hunan Cancer Hospital from January 2020 to November 2023. The clinical outcomes and prognosis factors for ICIs rechallenge were further analyzed.

Results

A total of 175 patients were included, of which 82(46.86 %) patients had primary resistance(PR) and 93(53.14 %) patients developed acquired resistance(AR). The progression-free survival(PFS), objective response rate (ORR), and disease control rate (DCR) of the total group were 3.3 months,16.57 %, and 53.71 %, respectively. The AR group exhibited significantly longer PFS compared to the PR group (4.5 months vs. 3.2 months, p = 0.012). In the PR group, a significantly longer PFS was found for ICIs rechallenge with interval treatment than without interval treatment(4.2 months vs. 3.1 months, p = 0.031). Within the AR group, the “new immunotherapy plus new chemotherapy” regimen showed a significantly longer PFS compared to the regimen of “maintain immunotherapy plus new chemotherapy” (8.3 months vs. 3.2 months, p = 0.014). The multivariate COX regression analyses demonstrated that both resistance pattern(p = 0.007) and treatment regimen(p = 0.039) independently served as risk factors for PFS in ICIs rechallenge.

Conclusion

Our study suggests that rechallenge of ICIs could be considered as a potential therapeutic strategy for advanced SCLC after progression from chemo-ICIs, particularly in patients with AR.

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一项现实世界的研究：ICIs对晚期小细胞肺癌在ICIs +化疗进展后的疗效再挑战

背景：在晚期小细胞肺癌（SCLC）中，对初始免疫检查点抑制剂（ICIs）加化疗（化疗-ICIs）产生耐药性后，具有挑战性的免疫检查点抑制剂（ICIs）仍不确定。方法回顾性研究纳入2020年1月至2023年11月湖南省肿瘤医院住院期间化疗化疗耐药后接受ICIs治疗的晚期SCLC患者。进一步分析ICIs再挑战的临床结局及预后因素。结果共纳入175例患者，其中原发性耐药（PR） 82例（46.86%），获得性耐药（AR） 93例（53.14%）。总组无进展生存期（PFS）为3.3个月，客观缓解率（ORR）为16.57%，疾病控制率（DCR）为53.71%。AR组的PFS明显长于PR组（4.5个月vs. 3.2个月，p = 0.012）。在PR组中，间隔治疗的ICIs再挑战的PFS明显长于未间隔治疗的PFS（4.2个月对3.1个月，p = 0.031）。在AR组中，“新免疫治疗+新化疗”方案的PFS明显长于“维持免疫治疗+新化疗”方案（8.3个月vs. 3.2个月，p = 0.014）。多因素COX回归分析显示，耐药模式（p = 0.007）和治疗方案（p = 0.039）分别是ICIs再挑战时PFS的危险因素。结论：我们的研究表明，ICIs的再挑战可以被认为是化疗ICIs进展后晚期SCLC的潜在治疗策略，特别是对于AR患者。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.