Association between immune-related adverse events and long-term survival outcomes in patients treated with immune checkpoint inhibitors

2020 ◽  
Vol 132 ◽  
pp. 61-70 ◽  
Author(s):  
Denis Maillet ◽  
Pauline Corbaux ◽  
Jean-Jacques Stelmes ◽  
Stéphane Dalle ◽  
Myriam Locatelli-Sanchez ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 989
Author(s):  
Heidar J. Albandar ◽  
Jacob Fuqua ◽  
Jasim M. Albandar ◽  
Salahuddin Safi ◽  
Samuel A. Merrill ◽  
...  

Introduction: There is growing recognition of immune related adverse events (irAEs) from immune checkpoint therapies being correlated with treatment outcomes in certain malignancies. There are currently limited data or consensus to guide management of irAEs with regards to treatment rechallenge. Methods: We conducted a retrospective analysis with an IRB-approved protocol of adult patients seen at the WVU Cancer Institute between 2011–2019 with a histopathologic diagnosis of active cancers and were treated with immune checkpoint inhibitors (ICI) therapy. Results: Demographics were similar between the ICI interrupted irAE groups within cancer types. Overall, out of 548 patients who received ICI reviewed, there were 133 cases of ≥1 irAE found of any grade. Being treated with anti-CTLA-4 inhibitor ICI was associated with lower risk of death compared to anti-PD-1 ICI. The overall survival difference observed for irAE positive patients, between rechallenged (37.8 months, reinitiated with/without interruption; 38.6 months, reinitiated after interruption) and interrupted/non-reinitiated (i.e., discontinued) groups (24.9 months) was not statistically significant, with a numerical trend favoring the former. Conclusions: Our exploratory study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.


Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1940 ◽  
Author(s):  
Maartje G. Schouwenburg ◽  
Karijn P.M. Suijkerbuijk ◽  
Rutger H.T. Koornstra ◽  
Anouk Jochems ◽  
Michiel C.T. van Zeijl ◽  
...  

The prognosis of patients with advanced melanoma has improved dramatically. However, the clinical outcomes of patients with highly elevated serum lactate dehydrogenase (LDH) remain very poor. The aim of this study was to explore whether patients with normalized LDH after targeted therapy could benefit from subsequent treatment with immune checkpoint inhibitors (ICI). Data from all patients with BRAF-mutant metastatic melanoma with a highly elevated serum LDH at baseline (≥2× upper limit of normal) receiving first-line targeted therapy between 2012 and 2019 in the Netherlands were collected. Patients were stratified according to response status to targeted therapy and change in LDH at start of subsequent treatment with ICI. Differences in overall survival (OS) between the subgroups were compared using log-rank tests. After a median follow-up of 35.1 months, median OS of the total study population (n = 360) was 4.9 months (95% CI 4.4–5.4). Of all patients receiving subsequent treatment with ICI (n = 113), survival from start of subsequent treatment was significantly longer in patients who had normalized LDH and were still responding to targeted therapy compared to those with LDH that remained elevated (median OS 24.7 vs. 1.1 months). Our study suggests that introducing ICI upon response to targeted therapy with normalization of LDH could be an effective strategy in obtaining long-term survival in advanced melanoma patients with initial highly elevated serum LDH.


2020 ◽  
Vol 9 (1) ◽  
pp. 223 ◽  
Author(s):  
Frank Gellrich ◽  
Marc Schmitz ◽  
Stefan Beissert ◽  
Friedegund Meier

Until recently, distant metastatic melanoma was considered refractory to systemic therapy. A better understanding of the interactions between tumors and the immune system and the mechanisms of regulation of T-cells led to the development of immune checkpoint inhibitors. This review summarizes the current novel data on the treatment of metastatic melanoma with anti-programmed cell death protein 1 (PD-1) antibodies and anti-PD-1-based combination regimens, including clinical trials presented at major conference meetings. Immune checkpoint inhibitors, in particular anti-PD-1 antibodies such as pembrolizumab and nivolumab and the combination of nivolumab with the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab can achieve long-term survival for patients with metastatic melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab were also approved for adjuvant treatment of patients with resected metastatic melanoma. Anti-PD-1 antibodies appear to be well tolerated, and toxicity is manageable. Nivolumab combined with ipilimumab achieves a 5 year survival rate of more than 50% but at a cost of high toxicity. Ongoing clinical trials investigate novel immunotherapy combinations and strategies (e.g., Talimogene laherparepvec (T-VEC), Bempegaldesleukin (BEMPEG), incorporation or sequencing of targeted therapy, incorporation or sequencing of radiotherapy), and focus on poor prognosis groups (e.g., high tumor burden/LDH levels, anti-PD-1 refractory melanoma, and brain metastases).


2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Anne Rogiers ◽  
Annelies Boekhout ◽  
Julia K. Schwarze ◽  
Gil Awada ◽  
Christian U. Blank ◽  
...  

Immune checkpoint inhibitors have become a standard of care option for the treatment of patients with advanced melanoma. Since the approval of the first immune checkpoint (CTLA-4) inhibitor ipilimumab in 2011 and programmed death-1 (PD-1) blocking monoclonal antibodies pembrolizumab and nivolumab thereafter, an increasing proportion of patients with unresectable advanced melanoma achieved long-term overall survival. Little is known about the psychosocial wellbeing, neurocognitive function, and quality of life (QOL) of these survivors. Knowledge about the long term side-effects of these novel treatments is scarce as long-term survivorship is a novel issue in the field of immunotherapy. The purpose of this review is to summarize our current knowledge regarding the survival and safety results of pivotal clinical trials in the field of advanced melanoma and to highlight potential long-term consequences that are likely to impact psychosocial wellbeing, neurocognitive functioning, and QOL. The issues raised substantiate the need for clinical investigation of these issues with the aim of optimizing comprehensive health care for advanced melanoma survivors.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 845.2-846
Author(s):  
T. Lenfant ◽  
L. Calabrese ◽  
C. Calabrese

Background:Immune Checkpoint inhibitors (ICI) have revolutionized cancer therapy by achieving remarkable survival benefits however, at the cost of a myriad of immune-related adverse events (irAEs)[1]. Rheumatic irAE can develop in 5-10% of patients although the true incidence is unknown given the lack of prospective studies [2]. Symptoms are heterogenous and probably underreported with few data available about their management and outcome [3].Objectives:To describe the clinical, biological, and radiological features of the largest cohort of rheumatic irAEs from ICI along with their therapeutic management, outcome and follow-up in real-world practice.Methods:A referral process for emergent rheumatic irAEs was initiated in February 2016 between the oncology and rheumatology departments at the Cleveland Clinic Foundation. All patients were evaluated by authors CC and/or LHC. Patients’ characteristics were retrospectively collected from medical charts after IRB approval.Results:70 patients referred for one or more rheumatic irAEs between February 2016 and January 2020 were included. 66% were male, median age was 60.8 years. Among them, 24 (34%) had pre-existing rheumatic complaints. Melanoma was the most frequent malignancy (56%). ICI therapy included anti-CTLA4 (40%), anti-PD1/L1 (79%), and dual therapy ipilimumab/nivolumab (41%). Rheumatic irAE occurred in a median 4 months after ICI initiation, with phenotypes including inflammatory arthritis (32 patients), sicca-like symptoms (12), polymyalgia rheumatica-like (7), and myositis (2). Oral, intravenous or intraarticular glucocorticoids (GC) were administered to 54 patients (77%). Of these 54 patients, 22 (41%) required long term GC, 19 had bone density scan and 15 received pneumocystis (PJP) prophylaxis. One PJP case, 1 osteoporotic fracture and 2 avascular necrosis cases were reported. 16 patients received conventional DMARDS (23%) and 9 received biologics (13%). ICI therapy was held for rheumatic irAE in 31% of cases and for another systemic irAE in 29%. Median follow-up was 13.6 months, at end of follow-up 51 patients were still on treatment for rheumatic irAE and 41% of them were still symptomatic despite ongoing treatment.Conclusion:Rheumatic irAEs are heterogeneous and often chronic requiring prolonged immunomodulatory therapy. Prospective studies are required to define optimal management of rheumatic irAEs that maintain long-term oncologic outcomes.References:[1]Suarez-Almazor ME, Kim ST, Abdel-Wahab N, Diab A. Review: Immune-Related Adverse Events With Use of Checkpoint Inhibitors for Immunotherapy of Cancer. Arthritis Rheumatol 2017;69:687–99.https://doi.org/10.1002/art.40043.[2]Abdel-Wahab N, Suarez-Almazor ME. Frequency and distribution of various rheumatic disorders associated with checkpoint inhibitor therapy. Rheumatol (United Kingdom) 2019;58:vii40–8.https://doi.org/10.1093/rheumatology/kez297.[3]Kostine M, Rouxel L, Barnetche T, Veillon R, Martin F, Dutriaux C, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: a single-centre prospective cohort study. Ann Rheum Dis 2018;77:393–8.https://doi.org/10.1136/annrheumdis-2017-212257.Disclosure of Interests:Tiphaine Lenfant: None declared, Leonard Calabrese Consultant of: AbbVie, GSK, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Sanofi, Horizon, Crescendo, and Gilead, Speakers bureau: Sanofi, Horizon, Crescendo, Novartis, Genentech, Janssen, and AbbVie, cassandra calabrese Consultant of: AbbvieGSK, Speakers bureau: Sanofi-Genzyme


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