Early Use of High-Dose Glucocorticoid for the Management of irAE Is Associated with Poorer Survival in Patients with Advanced Melanoma Treated with Anti–PD-1 Monotherapy

Bai, Xue; Hu, Jiani; Warner, Allison Betof; Quach, Henry T.; Cann, Christopher; Zhang, Michael Z.; Si, Lu; Tang, Bixia; Cui, Chuanliang; Yang, Xiaoling; Wei, Xiaoting; Pallan, Lalit; Harvey, Catriona; Manos, Michael P.; Ouyang, Olivia; Kim, Michelle S.; Kasumova, Gyulnara G.; Cohen, Justine V.; Lawrence, Donald P.; Freedman, Christine; Fadden, Riley; Rubin, Krista M.; Sharova, Tatyana; Frederick, Dennie T.; Flaherty, Keith T.; Rahma, Osama E.; Long, Georgina V.; Menzies, Alexander M.; Guo, Jun; Shoushtari, Alexander N.; Johnson, Douglas B.; Sullivan, Ryan J.; Boland, Genevieve M.

doi:10.1158/1078-0432.ccr-21-1283

Cited by 98 publications

(84 citation statements)

References 19 publications

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“… 37 When glucocorticoids were used to manage irAEs in advanced melanoma, early high-dose glucocorticoids were associated with decreased long-term outcomes. 38 However, pembrolizumab combined with carboplatin and paclitaxel or nab-paclitaxel achieved equivalent efficacy in KEYNOTE-407 trial for the first-line treatment of advanced lung squamous cell cancer. 39 Nab-paclitaxel is a nanoparticle albumin-bound form of paclitaxel.…”

Section: Discussionmentioning

confidence: 99%

Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma

Yang

Liu

et al. 2022

J Immunother Cancer

129

127

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BackgroundCamrelizumab and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the safety and efficacy of camrelizumab plus neoadjuvant chemotherapy, using pathologically complete response (pCR) as primary endpoint, in the treatment for locally advanced ESCC.MethodsPatients with locally advanced but resectable thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 1) plus nab-paclitaxel (100 mg/m2, day 1, 8, 15) and carboplatin (area under curve of 5 mg/mL/min, day 1) of each 21-days cycle, for two cycles before surgery. The primary endpoint is pCR rate in the per-protocol population. Safety was assessed in the modified intention-to-treat population that was treated with at least one dose of camrelizumab.ResultsFrom November 20, 2019 to December 22, 2020, 60 patients were enrolled. 55 (91.7%) patients completed the full two-cycle treatment successfully. 51 patients underwent surgery and R0 resection was achieved in 50 (98.0%) patients. pCR (ypT0N0) was identified in 20 (39.2%) patients and 5 (9.8%) patients had complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 58 patients (96.7%) had any-grade treatment-related adverse events (TRAEs), with the most common being leukocytopenia (86.7%). 34 patients (56.7%) had adverse events of grade 3 or worse, and one patient (1.7%) occurred a grade 5 adverse event. There was no in-hospital and postoperative 30-day as well as 90-day mortality.ConclusionsThe robust antitumor activity of camrelizumab and chemotherapy was confirmed and demonstrated without unexpected safety signals. Our findings established camrelizumab and chemotherapy as a promising neoadjuvant treatment for locally advanced ESCC.Trial registration numberChiCTR1900026240.

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Section: Discussionmentioning

confidence: 99%

Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma

Yang

Liu

et al. 2022

J Immunother Cancer

129

127

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“…As seen in our case, effective management of ICI-CeD centers on strict adherence to a gluten-free diet rather than initiation of systemic immunosuppression. This dietary change does not onlylead to the resolution of symptoms but also spares patients from systemic immunosuppression, which may reduce ICI efficacy ( 8 ). In addition to emphasizing the optimal treatment of ICI-CeD and the importance of including this toxicity in the differential diagnosis of potential GI toxicity, this case highlights the extraluminal manifestations of ICI-CeD.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Fulminant Celiac Disease With Combination Immune Checkpoint Therapy

et al. 2022

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Since the first approval of immune checkpoint inhibitors (ICIs) in 2011, these agents have rapidly become an integral treatment option across tumor types. However, with the increased adoption of ICIs, the incidence of immune-related adverse events (irAEs) continues to rise, and rare toxicity continues to be reported. Here, we present a case of a 70-year-old male patient with widespread metastatic melanoma who developed rapid onset anasarca and transaminitis after initiation of dual anti-PD-1/CTLA-4 inhibition with nivolumab and ipilimumab. An extensive workup was performed with serologies returning positive for anti-tissue transglutaminase immunoglobulin (tTG-IgA) and endoscopy revealing duodenal mucosal atrophy with duodenal biopsies confirming celiac disease. All symptoms resolved after initiation of a gluten-free diet without the addition of immunosuppression. This case highlights the importance of considering celiac disease in patients with suspected protein-losing enteropathy on ICI, the fulminant nature this uncommon irAE can present with, and underscores the broad differential clinicians must maintain when managing presumed irAEs.

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“…Despite the lack of robust evidence from randomized clinical trials, acute severe irAEs are managed with reasonable effectiveness by providing symptom management, withholding ICIs and administering high-dose glucocorticoids (or potentially other immunosuppressive medications for steroid-refractory irAEs) 59 – 61 . In general, high-dose glucocorticoids do not appear to interfere with antitumour responses, although data from several studies suggest that administration of steroids within a few weeks of starting treatment might result in inferior outcomes 42 , 62 , 63 .…”

Section: Timing and Resolutionmentioning

confidence: 99%

Immune-checkpoint inhibitors: long-term implications of toxicity

et al. 2022

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The development of immune-checkpoint inhibitors (ICIs) has heralded a new era in cancer treatment, enabling the possibility of long-term survival in patients with metastatic disease, and providing new therapeutic indications in earlier-stage settings. As such, characterizing the long-term implications of receiving ICIs has grown in importance. An abundance of evidence exists describing the acute clinical toxicities of these agents, although chronic effects have not been as well catalogued. Nonetheless, emerging evidence indicates that persistent toxicities might be more common than initially suggested. While generally low-grade, these chronic sequelae can affect the endocrine, rheumatological, pulmonary, neurological and other organ systems. Fatal toxicities also comprise a diverse set of clinical manifestations and can occur in 0.4–1.2% of patients. This risk is a particularly relevant consideration in light of the possibility of long-term survival. Finally, the effects of immune-checkpoint blockade on a diverse range of immune processes, including atherosclerosis, heart failure, neuroinflammation, obesity and hypertension, have not been characterized but remain an important area of research with potential relevance to cancer survivors. In this Review, we describe the current evidence for chronic immune toxicities and the long-term implications of these effects for patients receiving ICIs.

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Early Use of High-Dose Glucocorticoid for the Management of irAE Is Associated with Poorer Survival in Patients with Advanced Melanoma Treated with Anti–PD-1 Monotherapy

Cited by 98 publications

References 19 publications

Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma

Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma

Case Report: Fulminant Celiac Disease With Combination Immune Checkpoint Therapy

Immune-checkpoint inhibitors: long-term implications of toxicity

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