Dataset Information

Hyperprogressive disease under anti-PD-1 rechallenge after initial response to anti-PD-1 treatment for non-small cell lung cancer: a case report.

ABSTRACT:

Background

Hyperprogressive disease is an unexpected response pattern observed in immune checkpoint therapy and associated with poor prognosis. The rechallenge of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors can be a treatment option in non-small cell lung cancer (NSCLC) patients who once responded to them. Here, we reported the hyperprogressive phenomenon after PD-1/PD-L1 rechallenge in a patient with NSCLC.

Case description

This case report described a patient with recurrent large cell lung cancer undergoing hyperprogressive disease with pleural and pericardial dissemination shortly after the pembrolizumab rechallenge, although he had a favorable response to the initial pembrolizumab treatment. A lower ratio of CD8⁺ T cells to Foxp3⁺ regulatory T cells was distributed in the cell blocks of pleural and pericardial effusion which were taken after hyperprogressive disease, compared to the resected tumor microenvironment. Neutrophil-to-lymphocyte ratio (NLR) was lower in peripheral blood when the disease was controlled and it rose when the disease progressed. Notably, NLR increased dramatically when hyperprogression occurred.

Conclusions

For the first time, we reported that a patient who showed a favorable response to initial anti-PD-1 treatment underwent hyperprogressive disease when rechallenging the same immunotherapy. The increased Foxp3⁺ regulatory T cells in the tumor microenvironment and the longitudinal change of NLRs in peripheral blood were suggested to be associated with hyperprogressive disease.

SUBMITTER: Xu S

PROVIDER: S-EPMC11002506 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Hyperprogressive disease under anti-PD-1 rechallenge after initial response to anti-PD-1 treatment for non-small cell lung cancer: a case report.

Xu Shiting S Shukuya Takehito T Shimamura Shoko S Hayashi Takuo T Sato Yoshihiko Y Shiozaki Hitomi H Nishioki Toshihiko T Nishino Koichi K Kato Motoyasu M Hattori Aritoshi A Shimada Naoko N Suzuki Kenji K Kitano Shigehisa S Takahashi Kazuhisa K

Translational lung cancer research 20240327 3

<h4>Background</h4>Hyperprogressive disease is an unexpected response pattern observed in immune checkpoint therapy and associated with poor prognosis. The rechallenge of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors can be a treatment option in non-small cell lung cancer (NSCLC) patients who once responded to them. Here, we reported the hyperprogressive phenomenon after PD-1/PD-L1 rechallenge in a patient with NSCLC.<h4>Case description</h4>This case report desc ...[more]

PMID: 38601437

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Project description:BackgroundThe rechallenge of immune checkpoint inhibitors (ICI) is now an optional strategy for patients who discontinued ICI due to immune-related adverse events (irAEs) or disease progression. However, little data is available for the prognosis and prognostic factors of patients receiving ICI rechallenge treatment in advanced lung cancer patients. Our study aimed to explore the efficacy, prognosis and safety of patients who received anti-programmed cell death-1/programmed cell death ligand 1 (anti-PD-1/PD-L1) inhibitor rechallenge.MethodsIn our retrospective cohort study, data of advanced lung cancer patients who received anti-PD-1/PD-L1 inhibitor and discontinued due to irAEs or disease progression were collected from December 2016 to August 2021. Enrolled patients were categorized into two groups: rechallenge group (R group) and non-rechallenge group (NR group). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety data were analyzed. Cox model and subgroup analysis were analyzed according to baseline characteristics, ICI type, the reason for discontinuing ICI, etc. According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), evaluation was performed routinely every 6-8 weeks after initiating treatment with the PD-1/PD-L1 inhibitor. The last follow-up in the study was on September 20, 2021.ResultsEighty-one patients who met our inclusion criteria were enrolled. In the whole cohort, the R group achieved better OS than the NR group [hazard ratio (HR) =0.176; 95% confidence interval (CI): 0.065-0.477; P=0.001). In the irAEs group, the survival analyses showed a trend toward improved OS in the rechallenge subgroup (HR =0.287; 95% CI: 0.081-1.025; P=0.055), and a promising DCR of 75% after an ICI rechallenge. Additionally, the exploration of safety outcomes indicated an acceptable recurrence rate (22.5%) of irAEs and an early onset of irAEs after an ICI rechallenge. In the disease progression group, the rechallenge subgroup did not improve OS (HR =0.214; 95% CI: 0.027-1.695; P=0.144), and the DCR of the rechallenge subgroup was 40% after ICI rechallenge.ConclusionsICI rechallenge might be an attractive option for patients who discontinue treatment due to irAEs. For patients with disease progression, further research should be conducted. The recurrence of irAEs and their early onset during the second round of ICI should be considered.

Project description:ImportanceHyperprogressive disease (HPD) is a new pattern of progression recently described in patients with cancer treated with programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors. The rate and outcome of HPD in advanced non-small cell lung cancer (NSCLC) are unknown.ObjectivesTo investigate whether HPD is observed in patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors compared with single-agent chemotherapy and whether there is an association between treatment and HPD.Design, setting, and participantsIn this multicenter retrospective study that included patients treated between August 4, 2011, and April 5, 2017, the setting was pretreated patients with advanced NSCLC who received PD-1/PD-L1 inhibitors (8 institutions) or single-agent chemotherapy (4 institutions) in France. Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) on at least 2 computed tomographic scans before treatment and 1 computed tomographic scan during treatment was required.InterventionsThe tumor growth rate (TGR) before and during treatment and variation per month (ΔTGR) were calculated. Hyperprogressive disease was defined as disease progression at the first evaluation with ΔTGR exceeding 50%.Main outcomes and measuresThe primary end point was assessment of the HPD rate in patients treated with IO or chemotherapy.ResultsAmong 406 eligible patients treated with PD-1/PD-L1 inhibitors (63.8% male), 46.3% (n = 188) were 65 years or older, 72.4% (n = 294) had nonsquamous histology, and 92.9% (n = 377) received a PD-1 inhibitor as monotherapy in second-line therapy or later. The median follow-up was 12.1 months (95% CI, 10.1-13.8 months), and the median overall survival (OS) was 13.4 months (95% CI, 10.2-17.0 months). Fifty-six patients (13.8%) were classified as having HPD. Pseudoprogression was observed in 4.7% (n = 19) of the population. Hyperprogressive disease was significantly associated with more than 2 metastatic sites before PD-1/PD-L1 inhibitors compared with non-HPD (62.5% [35 of 56] vs 42.6% [149 of 350]; P = .006). Patients experiencing HPD within the first 6 weeks of PD-1/PD-L1 inhibitor treatment had significantly lower OS compared with patients with progressive disease (median OS, 3.4 months [95% CI, 2.8-7.5 months] vs 6.2 months [95% CI, 5.3-7.9 months]; hazard ratio, 2.18 [95% CI, 1.29-3.69]; P = .003). Among 59 eligible patients treated with chemotherapy, 3 (5.1%) were classified as having HPD.Conclusions and relevanceOur study suggests that HPD is more common with PD-1/PD-L1 inhibitors compared with chemotherapy in pretreated patients with NSCLC and is also associated with high metastatic burden and poor prognosis in patients treated with PD-1/PD-L1 inhibitors. Additional studies are needed to determine the molecular mechanisms involved in HPD.

Dataset Information

Hyperprogressive disease under anti-PD-1 rechallenge after initial response to anti-PD-1 treatment for non-small cell lung cancer: a case report.

Background

Case description

Conclusions

Publications

Hyperprogressive disease under anti-PD-1 rechallenge after initial response to anti-PD-1 treatment for non-small cell lung cancer: a case report.

Similar Datasets

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