Is Immune Checkpoint Inhibitor Treatment an Option for Patients With Rheumatic Diseases and Cancer?

Buckley, Lenore M.; Suarez‐Almazor, María E.

doi:10.1002/art.41064

Cited by 4 publications

(4 citation statements)

References 11 publications

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“… 49,50 Because chronic lymphocytic leukemia (CLL), lymphoma, and myeloma are associated with autoimmunity, 51 and because allogenic SCT is associated with graft-versus-host disease (GVHD), 50,52 the risk of ICIs triggering or exacerbating these pathological immune phenomena should be considered. 53 To date, this risk remains theoretical except possibly for patients with progressive CLL and recipients of allogeneic SCT. In 1 clinical trial of pembrolizumab for patients with R/R CLL or Richter transformation, about 20% of patients treated with ICIs suffered drug-related, but not demonstrably immune-mediated high-grade (CTCAE grades 3 to 4) anemia, thrombocytopenia, and/or neutropenia, 54 and acute GVHD (aGVHD) was more frequent among patients with lymphoid malignancies who received an allogeneic SCT after being treated with an ICI.…”

Section: Hematologic Toxicity Of Ici Treatment Of Hematologic Maligna...mentioning

confidence: 99%

Hematologic complications of immune checkpoint inhibitors

Kroll¹,

Yee²,

Rojas‐Hernandez

2022

Blood

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Immune checkpoint inhibitors are a class of anti-neoplastic therapies that unleash immune cells to kill malignant cells. There are currently 7 medications FDA-approved for the treatment of 14 solid tumors and 2 hematological malignancies. These medications commonly cause immune-related adverse effects due to overactive T lymphocytes, autoantibody production, and/or cytokine dysregulation. Hematological toxicities are rare and of uncertain mechanism, and therefore management is often based on experiences with familiar conditions involving these perturbed immune responses, such as autoimmune hemolytic anemia, immune thrombocytopenia, and idiopathic aplastic anemia. Management is challenging because one must attend to the hematological toxicity while simultaneously attending to the malignancy, with the imperative that effective cancer therapy be maintained or minimally interrupted if possible. The purpose of this review is to assist clinicians by providing a clinical and pathophysiological framework in which to view these problems.

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Section: Hematologic Toxicity Of Ici Treatment Of Hematologic Maligna...mentioning

confidence: 99%

Hematologic complications of immune checkpoint inhibitors

Kroll¹,

Yee²,

Rojas‐Hernandez

2022

Blood

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“…Anti-PD-1 drugs cause arthritis more frequently, and anti-CTLA-4 drugs are more related to colitis. 46 Combining anti-CTLA-4 antibodies and anti-PD-1 antibodies can increase the incidence and severity of irAEs and cause them to occur earlier. 47 This is consistent with our research findings.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of PD-1/PD-L1 plus CTLA-4 antibodies ± other therapies in lung cancer: a systematic review and meta-analysis

et al. 2021

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Purpose To investigate the efficacy and safety of programmed cell death 1 (PD-1)/programmed cell deathligand 1 (PD-L1) plus cytotoxic T lymphocyte antigen-4 (CTLA-4) antibodies ± other therapies in patients with advanced lung cancer. Methods In accordance with the retrieval strategy, we searched electronic databases for randomised controlled trials testing PD-1/PD-L1 plus CTLA-4 antibodies in patients with lung cancer; RR (for objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs)) from individual studies were calculated and pooled by using random-effects models or fixed-effects models; heterogeneity and publication bias analyses were also performed, using Review Manager 5.3 and Stata 15.1 for statistical analysis. Results We included six studies. Four different immune checkpoint inhibitors (nivolumab, pembrolizumab, durvalumab, tremelimumab) were used. Dual checkpoint inhibitors ± other therapies for advanced lung cancer showed significant improvements in ORR (RR 1.49, 95% CI 1.11 to 1.98; p=0.007), OS (HR 0.72, 95% CI 0.63 to 0.83; p<0.00001), and PFS (HR 0.72, 95% CI 0.63 to 0.82; p<0.00001). The subgroup analyses were consistent with the pooled results. The PD-L1 ≥1% (HR 0.67, 95% CI 0.54 to 0.82; p<0.0001) subgroup differences indicated a statistically significant subgroup effect, but the PD-L1 <1% subgroup (HR 0.88, 95% CI 0.75 to 1.05; p=0.15) was not statistically significant. The incidence of adverse events (grade ≥3) was lower than that of the control group (RR 0.90, 95% CI 0.80 to 1.02; p=0.09), but was not significant. Conclusions PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors ± other therapies can improve the ORR, OS and PFS of patients with advanced or metastatic lung cancer, but the incidence of adverse reactions is high although generally tolerable.

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“…58 The organ involvement spectrum of the two is also different, anti-PD-1 drugs cause arthritis more frequently, and anti-CTLA-4 drugs are more related to colitis. 59 Combining anti-CTLA-4 antibodies and anti-PD-1 antibodies can increase the incidence and severity of irAEs and occur earlier. 60 This is consistent with our research finding.…”

Section: Discussionmentioning

confidence: 99%

“…61 Receiving low-dose glucocorticoids does not inhibit the immune response caused by ICIS, and can continue and maintain a beneficial response to ICIs. 59 The combination of anti-PD-1 antibodies and immune antibodies of selectively target specific inflammatory mediators can prevent or delay the progression of advanced tumors with autoimmune diseases without affecting the anti-tumor effect of anti-PD-1 antibodies. 62 It was observed that even if patients receiving PD-1 antibodies stopped treatment due to the reaction, they could have a longer duration of action without the need to rush to the next treatment.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of PD-1/PD-L1 plus CTLA-4 antibodies +/− Other Therapies in Lung Cancer: A Systematic Review and Meta-Analysis

Shen

Huang

Liu

et al. 2020

Preprint

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BackgroundImmune checkpoint inhibitors have brought hope for patients with advanced lung cancer, among which PD-1/PD-L1 and CTLA-4 inhibitors have achieved considerable results. This meta-analysis aims to investigate the efficacy and safety of PD-1/PD-L1 combined with CTLA-4 antibodies in patients with advanced lung cancer.Materials and MethodsRandomized controlled trials (RCTs) study of PD-1/PD-L1 combined with CTLA-4 inhibitors for advanced lung cancer was searched in the database for systematic review and meta-analysis.ResultsThe meta-analysis finally included 4 trials (actually 3 trials), and the results showed that the overall response rate of PD-1/PD-L1 combined with CTLA-4 inhibitor was higher than that of the control group (ORR = 2.29 [95% CI 1.58 3.32], P <0.0001). PFS significantly improved compared with conventional treatment (HR = 0.69 [95% CI 0.56, 0.85], P = 0.0005), which was statistically significant. OS also improved but did not statistically significant (HR = 0.80 [95% CI 0.61, 1.05], P = 0.11). PD-1/PD-L1 combined with CTLA-4 inhibitors had a higher incidence of adverse reactions than conventional treatment (OR = 1.72 [95% CI 0.59, 5.09], P = 0.33), but the incidence of grade≥3 AEs was lower than the control group (OR = 0.96 [95% CI 0.64, 1.44], P = 0.85).ConclusionDouble checkpoint inhibitor PD-1/PD-L1 combined with CTLA-4 antibody has synergistic anti-cancer activity and improved ORR and PFS in lung cancer. Adverse reactions are more common than conventional treatment, but are generally controllable. Therefore, PD-1/PD-L1 combined with CTLA-4 inhibitors provides a beacon for the treatment of advanced lung cancer, which has guiding significance for the treatment selection in the future.

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Is Immune Checkpoint Inhibitor Treatment an Option for Patients With Rheumatic Diseases and Cancer?

Cited by 4 publications

References 11 publications

Hematologic complications of immune checkpoint inhibitors

Hematologic complications of immune checkpoint inhibitors

Efficacy and safety of PD-1/PD-L1 plus CTLA-4 antibodies ± other therapies in lung cancer: a systematic review and meta-analysis

Efficacy and Safety of PD-1/PD-L1 plus CTLA-4 antibodies +/− Other Therapies in Lung Cancer: A Systematic Review and Meta-Analysis

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