Clinical difference between discontinuation and retreatment with nivolumab after immune-related adverse events in patients with lung cancer

Mouri, Atsuto; Kaira, Kyoichi; Yamaguchi, Ou; Shiono, Ayako; Miura, Yu; Hashimoto, Kosuke; Nishihara, Fuyumi; Murayama, Yoshitake; Kobayashi, Kunihiko; Kagamu, Hiroshi

doi:10.1007/s00280-019-03926-y

Cited by 33 publications

(48 citation statements)

References 11 publications

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“…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%

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: 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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“…Previous research on patients with NSCLC for whom nivolumab was discontinued due to irAE, explored the clinical differences between discontinuation and retreatment with nivolumab. The median overall survival (OS) and progression-free survival (PFS) did not differ significantly between retreatment and discontinuation in both studies [12,13]. Mouri et al reported that the median OS and PFS did not differ significantly between retreatment and discontinuation.…”

Section: Discussionmentioning

confidence: 98%

“…However, the disadvantages of CT include radiation exposure and limited availability [10,11,15,16]. On the other hand, the myriad advantages of US include lack of radiation exposure, non-invasiveness, and costeffectiveness [12,17]. US has recently garnered interest as a useful imaging modality for the diagnosis and follow-up of inflammatory bowel disease [4,[13][14][15][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Induced Colitis Successfully Followed up by Ultrasonography

Omotehara

Nishida

Nagashima

et al. 2020

SN Compr. Clin. Med.

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Nivolumab is an immune checkpoint inhibitor (ICI), which is used for treatment of advanced malignancies. Diarrhea is a typical adverse effect of ICIs. Several endoscopic features of ICI-related colitis have been reported. Herein, we reported a case of ICI-related colitis, with successful follow-up using ultrasonography (US). A 54-year-old woman, diagnosed with renal cell carcinoma, underwent radical nephrectomy. Multiple liver and bone metastases appeared 6 months after surgery. She was prescribed sunitinib, which was discontinued, because of severe diarrhea. She was prescribed nivolumab after 1 week. However, she was hospitalized 9 days later, due to fever and diarrhea. US showed diffuse wall thickening from the cecum to the rectum. The wall layer structures were preserved, and thickening was observed mainly in the submucosa, but not in the mucosa, without a decrease in the echo level. Subsequently, sigmoidoscopy was performed. Severe edema was observed in the mucosa, without any erosion and granularity. She was clinically diagnosed with ICI-related colitis, and steroid therapy was administered. One week after steroid therapy, the diarrhea improved, and the earlier findings showed marked improvement on US. After another week of reduced steroid dose, US revealed further improvement, and she was discharged. Keywords Immune checkpoint inhibitor. Nivolumab. Immune-related adverse effect. Colitis. Ultrasonography This article is part of the Topical Collection on Imaging

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“…In the priming phase, anti-PD-L1 may also promote T-cell priming and activation more strongly than anti-PD-1 (14,15). Furthermore, in previous studies, patients were rechallenged with the ICIs used in the initial treatment that had induced irAEs (3,5). Switching from anti-PD-1 to anti-PD-L1 might be suitable in terms of an improved efficacy and safety.…”

Section: Discussionmentioning

confidence: 99%

“…Among all irAEs, renal dysfunction is relatively rare ( 1 ). The recurrence rate of irAEs was 39-71.4% when ICIs were readministered to patients who discontinued the use of ICIs because of irAEs ( 2 - 5 ). There are few reports on the safety and efficacy of programmed cell death-ligand 1 antibody (anti-PD-L1) in patients who discontinued the use of programmed cell death-1 antibody (anti-PD-1) because of irAEs.…”

Section: Introductionmentioning

confidence: 99%

Successful Treatment of Non-small-cell Lung Cancer with Atezolizumab Following Tubulointerstitial Nephritis Due to Pembrolizumab

et al. 2020

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We herein report a 75-year-old man with non-small-cell lung cancer who developed tubulointerstitial nephritis due to pembrolizumab administration. He was successfully treated with atezolizumab following steroid administration. He was initially diagnosed with lung adenocarcinoma (T1bN3M1b, stage IV), with a programmed cell death-ligand 1 tumor proportion score of 25-49%. Although the tumor responded well to pembrolizumab, the drug was discontinued because of the diagnosis of tubulointerstitial nephritis on a renal biopsy. Tubulointerstitial nephritis was treated with 30 mg prednisolone, the dose of which was tapered to and maintained at 5 mg. Following lung cancer progression, atezolizumab was administered, and the tumor responded again. Its efficacy has been sustained for >15 months without recurrence of tubulointerstitial nephritis.

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Clinical difference between discontinuation and retreatment with nivolumab after immune-related adverse events in patients with lung cancer

Cited by 33 publications

References 11 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

Immune Checkpoint Inhibitor-Induced Colitis Successfully Followed up by Ultrasonography

Successful Treatment of Non-small-cell Lung Cancer with Atezolizumab Following Tubulointerstitial Nephritis Due to Pembrolizumab

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