Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer

Dolladille, Charles; Éderhy, Stéphane; Sassier, Marion; Cautela, Jennifer; Thuny, Franck; Fédrizzi, Sophie; Chrétien, Basile; Silva, Angélique Da; Plane, Anne-Flore; Legallois, Damien; Milliez, Paul; Lelong‐Boulouard, Véronique; Alexandre, Jonas

doi:10.1001/jamaoncol.2020.0726

Cited by 364 publications

(368 citation statements)

References 23 publications

(58 reference statements)

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“…This study showed no statistically significant difference in the incidence of irAEs, and the irAE profile was similar in both groups. 41 Another study evaluating safety and efficacy of ICI treatment in real life conditions showed no difference in OS, PFS, or irAEs between patients older than 70 years old or younger patients. 84 However, Baldini et al analysed patients treated with anti-PDL-1 therapy and showed an increase in the incidence of grade 2 or higher AEs in patients older than 70 years (33% versus 25%, p = 0.03).…”

Section: Immunotherapy In High Risk Populations Patients With Auto Immentioning

confidence: 99%

“…Recently Dolladille et al 41 descrip a pharmacovigilance cohort of of 24,079 irAEs associated with at least one ICI and 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were analysis. This cohort study find 28.8% of recurrence rate of the same irAE.…”

Section: Resuming Ici Treatmentmentioning

confidence: 99%

“…Moreover, older patients are known to have a higher prevalence of auto-antibodies and one can also expect that ICI treatment may reveal subclinical autoimmune diseases. 41 A meta-analysis of randomised trials was conducted to investigate the efficacy of ICI treatment in older patients compared to younger adults. The efficacy of anti-CTLA-4 or anti-PD-1/PDL-1 therapy for different indications was analysed in 1244 older patients and compared to 2078 younger patients.…”

Section: Immunotherapy In High Risk Populations Patients With Auto Immentioning

confidence: 99%

“…Patients treated with anticoagulant or antiplatelet therapy must be carefully monitored in cases where colitis symptoms are identified, given the risk of gastrointestinal hemorrhage. 41 Moreover, the use of some symptomatic treatments such as antihistamine for pruritus or corticosteroids may expose older patients to iatrogenic events such as worsening diabetes, disturbed mental status, hypertension, and delirium. 41 A geriatric assessment could help identify older patients who will benefit from ICI treatment.…”

Section: Immunotherapy In High Risk Populations Patients With Auto Immentioning

confidence: 99%

“…41 Moreover, the use of some symptomatic treatments such as antihistamine for pruritus or corticosteroids may expose older patients to iatrogenic events such as worsening diabetes, disturbed mental status, hypertension, and delirium. 41 A geriatric assessment could help identify older patients who will benefit from ICI treatment. 86 Since half of all malignancies are diagnosed in patients older that 65 years old, dedicated studies are necessary for the proper and safe use of ICI treatment in the older patient population.…”

Section: Immunotherapy In High Risk Populations Patients With Auto Immentioning

confidence: 99%

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<p>Management of Immune Checkpoint Inhibitor Toxicities</p>

Durrechou¹,

Domblides²,

Sionneau³

et al. 2020

CMAR

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Immune checkpoint inhibitors (ICIs) have radically changed the clinical outcome of several cancers with durable responses. CTLA-4 (cytotoxic T lymphocyte antigen-4), PD-1 (programmed cell death protein 1) or PDL-1 (programmed cell death ligand protein 1) represent ICIs that can be used as monotherapy or in combination with other agents. The toxicity p\rofiles of ICIs differ from the side effects of cytotoxic agents and come with new toxicities like immune-related adverse events. Typically, these toxicities occur in all organs. However, the main organs affected are the skin, digestive, hepatic, lungs, rheumatologic, and endocrine. Most of the immune toxicity that occurs is low grade but some more severe toxicities can occur that require a rapid diagnosis and appropriate treatment. The recognition of symptoms by physicians and patient is necessary to resolve them rapidly and adapt treatment to allow the toxicity to resolve.

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Section: Immunotherapy In High Risk Populations Patients With Auto Immentioning

confidence: 99%

Section: Resuming Ici Treatmentmentioning

confidence: 99%

Section: Immunotherapy In High Risk Populations Patients With Auto Immentioning

confidence: 99%

Section: Immunotherapy In High Risk Populations Patients With Auto Immentioning

confidence: 99%

Section: Immunotherapy In High Risk Populations Patients With Auto Immentioning

confidence: 99%

See 3 more Smart Citations

<p>Management of Immune Checkpoint Inhibitor Toxicities</p>

Durrechou¹,

Domblides²,

Sionneau³

et al. 2020

CMAR

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Overall Survival, Treatment Duration, and Rechallenge Outcomes With ICI Therapy for Recurrent or Metastatic HNSCC

Sun,

Cohen,

D’Avella

et al. 2024

JAMA Netw Open

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ImportanceImmune checkpoint inhibition (ICI) is a frontline treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but questions remain surrounding optimal duration of therapy, benefits and risks of ICI rechallenge, and efficacy in first vs subsequent lines of therapy.ObjectivesTo estimate survival in US patients receiving ICI-based treatment for R/M HNSCC, compare outcomes associated with treatment discontinuation vs continuation at 1 or 2 years, and assess outcomes after immunotherapy rechallenge.Design, Setting, and ParticipantsThis retrospective, population-based cohort study included adult patients in the Flatiron Health nationwide oncology database treated with immunotherapy for R/M HNSCC from 2015 to 2023. Data cutoff was August 31, 2023; data analysis was conducted from December 2023 to February 2024.ExposuresTreatment continuation vs discontinuation at 1 and 2 years; rechallenge with ICI after at least a 60-day period off ICI therapy without intervening systemic treatment (immediate rechallenge), or with intervening systemic treatment (delayed rechallenge).Main Outcomes and MeasuresOverall survival (OS) from ICI initiation was analyzed using the Kaplan-Meier method. Cox multivariable regression was used to examine associations of key variables (line of therapy, human papillomavirus [HPV] status, Eastern Cooperative Oncology Group [ECOG] performance status) with survival.ResultsThe cohort included 4549 patients with R/M HNSCC who received ICI-containing therapy (median [IQR] age, 66 [59-72] years; 3551 [78.1%] male; 56 [1.2%] Asian, 260 [5.7%] Black or African American, 3020 [66.4%] White, 1213 [26.7%] other or unknown race; 3226 [70.9%] ECOG performance status 0 or 1). There were 3000 patients (65.9%) who received ICI in frontline and 1207 (26.5%) in second line; 3478 patients (76.5%) received ICI monotherapy. Median (IQR) OS was 10.9 (4.1-29.1) months and was longer in patients who received ICI in frontline therapy (12.2 [4.8-32.0] vs 8.7 [3.2-22.4] months), had HPV-positive cancer (16.6 [6.5-43.9] vs 8.8 [3.5-24.0] months), and had ECOG performance status 0 or 1 (13.5 [5.2-33.9] vs 5.5 [2.0-13.7] months). There were no survival differences on adjusted analysis between patients who stopped vs those who continued ICI at 1 or 2 years. Median (IQR) OS after ICI rechallenge was 15.7 (13.7-21.9) months in the immediate rechallenge group and 9.9 (3.7-18.1) months in the delayed rechallenge group.Conclusions and RelevanceIn this large cohort study of patients with R/M HNSCC receiving ICI-based therapy, survival estimates closely mirrored clinical trial results, both in frontline and later-line settings. Discontinuation of ICI in long-term responders at 1 or 2 years may be a reasonable strategy that does not appear to compromise survival. ICI rechallenge was associated with clinical benefit in a subset of patients.

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Recurrence of Immune-Related Adverse Events After Immune Checkpoint Inhibitor Rechallenge

2020

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To the Editor Recently, with the increasing research on immunerelated adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs), recurrence of irAEs after ICI rechallenge has deserved more attention. In their cohort study, Dolladille and colleagues 1 retrospectively assessed safety in patients with cancer who resumed therapy with the same ICIs and found that ICI rechallenge was associated with a recurrence of the same irAEs in one-quarter to one-third of the cases. However, there are some suggestions of this study that ought to be carefully considered, especially considering its promising research future as to ICIs.First, this study included patients with all kinds of cancers. But different varieties of cancers do not have similar rates of various irAEs. 2,3 Also, not all cancer types could achieve significant efficacy from ICIs, which means it is very important to evaluate the balance between the risk of irAEs and the efficacy of ICIs. 4 As a result, we suggest further exploration of between-study heterogeneity by subgrouping studies according to different cancer types. Second, this research compared the irAE rate between rechallenge and nonrechallenge cases but only reported the time to onset of initial irAEs, ignoring the time between recurrence of irAEs and ICI rechallenge, which is worthy of comparison. Third, this study evaluated the recurrence rate by dividing the number of cases with an irAE recurrence by the number of informative rechallenges. 1 However, they only included cases with a rechallenge with the same ICI drug after a first irAE, ignoring patients who had irAEs 2 or more times. Therefore, it is deficient to draw a conclusion from that calculation; it would be better regarded as a conditional conclusion. In closing, as to the suggestions enumerated above, further analysis is needed to obtain more valuable and rigorous conclusions.

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Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer

Cited by 364 publications

References 23 publications

<p>Management of Immune Checkpoint Inhibitor Toxicities</p>

<p>Management of Immune Checkpoint Inhibitor Toxicities</p>

Overall Survival, Treatment Duration, and Rechallenge Outcomes With ICI Therapy for Recurrent or Metastatic HNSCC

Recurrence of Immune-Related Adverse Events After Immune Checkpoint Inhibitor Rechallenge

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