Outcomes of long-term responders to anti-programmed death 1 and anti-programmed death ligand 1 when being rechallenged with the same anti-programmed death 1 and anti-programmed death ligand 1 at progression

Bernard‐Tessier, Alice; Baldini, Capucine; Martín, Patricia; Champiat, Stéphane; Hollebecque, Antoine; Postel-Vinay, Sophie; Varga, Andréa; Bahleda, Rastilav; Gazzah, Anas; Michot, Jean‐Marie; Ribrag, Vincent; Armand, Jean‐Pierre; Marabelle, Aurélien; Soria, Jean‐Charles; Massard, Christophe

doi:10.1016/j.ejca.2018.06.005

Cited by 54 publications

(63 citation statements)

References 15 publications

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“…This phenomena has not be studied in detail. Though others report the potential for a response with CPI rechallenge, 19 this is the first report, to our knowledge, of disease response on CPI rechallenge in mesothelioma.…”

Section: Laboratory Correlates Of Immune Responsementioning

confidence: 69%

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab

Minchom

Yuan

Gürel

et al. 2020

J Immunother Cancer

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BackgroundThis case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge.Case presentationA 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved. Serial biopsies and analysis by immunohistochemistry and immunofluorescence demonstrated marked immune infiltration and documented the emergency of markers of immune exhaustion. Whole exome sequencing demonstrated a reduction in tumor mutational burden consistent with subclone elimination by immune checkpoint inhibitor (CPI) therapy. The relapse biopsy had missense mutation in BTN2A1.ConclusionThis case supports rechallenge of programme death receptor 1 inhibitor in cases of previous CPI sensitivity and gives molecular insights.

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Section: Laboratory Correlates Of Immune Responsementioning

confidence: 69%

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab

Minchom

Yuan

Gürel

et al. 2020

J Immunother Cancer

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“…One possibility is that epigenetic repression of a neoantigen in a lung cancer expressed gene may result at a fitness cost. This may shed light on recent phenomenon observed in some patients with acquired resistance to checkpoint inhibitor therapy, who are subsequently re-challenged with the same drug and respond a second time 26 .…”

Section: Discussionmentioning

confidence: 82%

Neoantigen-directed immune escape in lung cancer evolution

Rosenthal

Cadieux

Salgado

et al. 2019

Nature

688

615

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“…We did not find any prospective trial published on this issue and we identified 14 full papers (five case reports and nine case series) reporting the outcomes of 74 patients treated according to this strategy ( Fig. 1, Table 1) (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Data search ended the 25th January 2020.…”

Section: Methodsmentioning

confidence: 99%

Literature meta-analysis about the efficacy of anti-programmed death protein 1 and anti-programmed death ligand 1 re-challenge in cancer patients

Gobbini¹,

Charles²,

Toffart³

et al. 2020

Preprint

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Background Immune checkpoint inhibitor (ICPis) re-challenge could be an attractive therapeutic option considering its good safety profile. However, little data is available regarding anti-PD-1/anti-PD-L1 retreatment. We conducted a meta-analysis focusing on outcomes of solid cancer patients performing this strategy. Methods Fourteen full papers involving 74 patients were included. Individual data about best response or progression-free survival (PFS) upon the first and second course of anti-PD-1/ anti-PD-L1 were collected. Results Non-small-cell lung cancer (53%) and melanoma (34%) were the most represented cancers. Higher objective response (46% versus 24%, p = 4.10 -4 ) and disease control rates (73% versus 52%, p = 7.10 -3 ) were obtained upon the first ICPi course compared to re-challenge. No association between responses obtained with the two ICPis courses was found ( p = 3.10 -1 ). The PFS upon the first ICPi (PFS1) was longer than that after re-challenge (PFSR) (6.6 versus 2.8 months, hazard ratio (HR) 0.57, p = 2.10 -3 ). A longer PFSR was obtained in patients with a longer PFS1 ( p = 6.10 -3 ), in those who discontinued the first ICPi due to toxicity or per protocol (8.8 versus 2.1 months if disease progression occurs, p = 2.10 -3 ), and in those not receiving intercalated treatment between the two ICPis (6.6 versus 2.1 months for the treated ones, p = 1.10 -3 ). Conclusion Anti-PD-1/anti-PD-L1 re-challenge showed interesting clinical activity in selected patients, mainly in those achieving a long-term response upon the first ICPi course, that do not discontinue therapy because of disease progression, or that are able to keep a treatment-free period.

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Outcomes of long-term responders to anti-programmed death 1 and anti-programmed death ligand 1 when being rechallenged with the same anti-programmed death 1 and anti-programmed death ligand 1 at progression

Cited by 54 publications

References 15 publications

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab

Neoantigen-directed immune escape in lung cancer evolution

Literature meta-analysis about the efficacy of anti-programmed death protein 1 and anti-programmed death ligand 1 re-challenge in cancer patients

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