Evaluation of Readministration of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer

Simonaggio, Audrey; Michot, Jean‐Marie; Voisin, Anne Laure; Pavec, Jérôme Le; Collins, Michael; Lallart, A.; Cengizalp, Geoffray; Vozy, Aurore; Laparra, Ariane; Varga, Andréa; Hollebecque, Antoine; Champiat, Stéphane; Marabelle, Aurélien; Massard, Christophe; Lambotte, Olivier

doi:10.1001/jamaoncol.2019.1022

Cited by 300 publications

(251 citation statements)

References 26 publications

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“…Rechallenging patients with ICIs after discontinuation for toxicity resulted in another irAE (new or recurrent) in 50% of patients with mRCC, which was similar to published data from small series in melanoma, NSCLC, lymphoma and other solid tumors (50%-55%). [17][18][19] However, these irAEs appear to be manageable with no grade 4 toxicity or treatment-related deaths in our experience. Clinicians were no doubt more vigilant about toxicity monitoring in patients retreated with ICIs, and, in our study, tended to discontinue therapy on new or recurrent onset of irAEs after retreatment (72.2%), irrespective of the irAE grade.…”

Section: Discussionmentioning

confidence: 60%

“…The literature is scarce regarding restarting ICI therapy after recovery from high-grade irAEs and is mostly derived from experiences in melanoma and non-small cell lung cancer (NSCLC), with no reported studies in RCC. [16][17][18][19][20] The overarching objective of this international, multicenter collaboration was to characterize the safety and efficacy of restarting ICI therapy after a clinically significant irAE, defined as one requiring treatment interruption or discontinuation, in patients with mRCC.…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma

Alaiwi

Xie

Nassar

et al. 2020

J Immunother Cancer

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BackgroundImmune checkpoint inhibitors (ICI) induce a range of immune-related adverse events (irAEs) with various degrees of severity. While clinical experience with ICI retreatment following clinically significant irAEs is growing, the safety and efficacy are not yet well characterized.MethodsThis multicenter retrospective study identified patients with metastatic renal cell carcinoma treated with ICI who had >1 week therapy interruption for irAEs. Patients were classified into retreatment and discontinuation cohorts based on whether or not they resumed an ICI. Toxicity and clinical outcomes were assessed descriptively.ResultsOf 499 patients treated with ICIs, 80 developed irAEs warranting treatment interruption; 36 (45%) of whom were restarted on an ICI and 44 (55%) who permanently discontinued. Median time to initial irAE was similar between the retreatment and discontinuation cohorts (2.8 vs 2.7 months, p=0.59). The type and grade of irAEs were balanced across the cohorts; however, fewer retreatment patients required corticosteroids (55.6% vs 84.1%, p=0.007) and hospitalizations (33.3% vs 65.9%, p=0.007) for irAE management compared with discontinuation patients. Median treatment holiday before reinitiation was 0.9 months (0.2–31.6). After retreatment, 50% (n=18/36) experienced subsequent irAEs (12 new, 6 recurrent) with 7 (19%) grade 3 events and 13 drug interruptions. Median time to irAE recurrence after retreatment was 2.8 months (range: 0.3–13.8). Retreatment resulted in 6 (23.1%) additional responses in 26 patients whose disease had not previously responded. From first ICI initiation, median time to next therapy was 14.2 months (95% CI 8.2 to 18.9) and 9.0 months (5.3 to 25.8), and 2-year overall survival was 76% (95%CI 55% to 88%) and 66% (48% to 79%) in the retreatment and discontinuation groups, respectively.ConclusionsDespite a considerable rate of irAE recurrence with retreatment after a prior clinically significant irAE, most irAEs were low grade and controllable. Prospective studies are warranted to confirm that retreatment enhances survival outcomes that justify the safety risks.

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma

Alaiwi

Xie

Nassar

et al. 2020

J Immunother Cancer

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“…In the case of immunotherapy, the mechanism of action, involving resetting the immune memory, and the possibility of predicting clinical response from biomarkers [21,22], the notion of a second course of immunotherapy is an attractive one. Retreatment with PD-1 inhibitor, as a subsequent therapy, has been reported in limited numbers of patients in randomised clinical trials of nivolumab or pembrolizumab in NSCLC [19,23,24] and there are a limited number of reports of rechallenge with immunotherapy, which have generally involved small numbers of patients [25][26][27][28][29][30][31]. Regarding the relative benefit of rechallenge compared to the initial treatment course, the available data are encouraging [27,28] even though no definitive conclusions can be drawn given the limited experience and the heterogeneity in the definitions of retreatment and in the protocols used.…”

mentioning

confidence: 99%

“…Regarding the relative benefit of rechallenge compared to the initial treatment course, the available data are encouraging [27,28] even though no definitive conclusions can be drawn given the limited experience and the heterogeneity in the definitions of retreatment and in the protocols used. Importantly, in patients restarting PD-1 inhibitor after discontinuation due to the occurrence of an adverse event, safety seems acceptable [29,30].…”

mentioning

confidence: 99%

Immunotherapy rechallenge after nivolumab treatment in advanced non-small cell lung cancer in the real-world setting: A national data base analysis

Levra¹,

Cotté²,

Corre³

et al. 2020

Lung Cancer

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Nivolumab is now a reference treatment for patients with advanced non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. Little data are available on treatment approaches following discontinuation of nivolumab and on the interest of a second course of immunotherapy after nivolumab discontinuation. The aims of this study were to describe treatment pathways following nivolumab discontinuation and to describe survival following retreatment with immunotherapy. Materials and methods: The analysis includes all patients with NSCLC recorded in a national hospital database, starting nivolumab in 2015-2016. Nivolumab treatment was considered discontinued if ≥3 infusions were missed. Patients starting a second course of PD-1 inhibitor following nivolumab discontinuation were analysed according to the duration of their initial nivolumab treatment course. Results: 10,452 patients were included (71 % men; mean age: 63.8 ± 9.6 years; squamous histology: 44 %). Median nivolumab treatment duration was 2.8 months [IQR :1.4-6.9]. Median OS was 11.5 months [95 %CI: 11.1-11.9]; 5118 (53.4 %) patients received post nivolumab therapy lines: 1517 (29.6 %) of these received a second course of PD-1 inhibitor, either after a treatment-free interval (resumption: n = 1127) or after intervening chemotherapy (rechallenge: n = 390). Median OS after nivolumab discontinuation was 15.0 months [13.9-16.7] in the resumption group and 18.4 months [14.8-21.9] in the rechallenge group. Median OS was significantly longer in patients with an initial nivolumab treatment duration ≥3 months. Conclusion: In this real-world setting, outcome after retreatment with a PD-1 inhibitor following a first course of nivolumab was significantly better in patients with a longer duration of initial nivolumab treatment.

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“…The drug-free period is recommended until the symptoms are resolved and the eventual steroid treatment is completed. According to the results of retrospective studies patients who restarted ICIs had a 30-60% of risk of recurrence of the same irAE or of a new one; no clear benefit in terms of progression-free survival, or overall survival, were demonstrated [18][19][20][21]. For grade ≥ 2 diarrhea/colitis, American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) guidelines recommend high dose steroid-therapy or infliximab in case of steroid-refractory diarrhea [3,13].…”

Section: Treatment Of Gastrointestinal Toxicitymentioning

confidence: 99%

Imaging of Adverse Events Related to Checkpoint Inhibitor Therapy

et al. 2020

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Immunotherapy with checkpoint inhibitors (ICIs) is becoming standard of practice for an increasing number of cancer types. ICIs enhance T-cell action against the cancer cells. By unbalancing the immune system ICIs may cause dysimmune toxicities, a series of disorders broadly defined immune-related adverse events (irAEs). IrAEs may affect any organ or apparatus and most frequently involve skin, colon, endocrine organs, liver, and lungs. Early identification and appropriate treatment of irAEs can improve patient outcome. The paper aims at reviewing mechanisms of the occurrence of irAEs, the importance of a proper diagnosis and the main pillars of therapy. To provide effective guidance to the comprehension of major irAEs imaging findings will be reviewed.

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Evaluation of Readministration of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer

Cited by 300 publications

References 26 publications

Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma

Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma

Immunotherapy rechallenge after nivolumab treatment in advanced non-small cell lung cancer in the real-world setting: A national data base analysis

Imaging of Adverse Events Related to Checkpoint Inhibitor Therapy

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