Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology

Thompson, John A.; Schneider, Bryan J.; Brahmer, Julie R.; Achufusi, Amaka; Armand, Philippe; Berkenstock, Meghan; Bhatia, Shailender; Budde, Lihua E.; Chokshi, Saurin; Davies, Marianne; Elshoury, Amro; Gesthalter, Yaron; Hegde, Aparna; Jain, Michael D.; Kaffenberger, Benjamin H.; Lechner, Melissa G.; Li, Tianhong; Marr, Alissa S.; McGettigan, Suzanne; McPherson, Jordan P.; Medina, Theresa; Mohindra, Nisha; Olszanski, Anthony J.; Oluwole, Olalekan O.; Patel, Sandip Pravin; Patil, Pradnya D.; Reddy, Sunil; Ryder, Mabel; Santomasso, Bianca; Shofer, Scott; Sosman, Jeffrey A.; Wang, Yinghong; Zaha, Vlad G.; Lyons, Megan; Dwyer, Mary A.; Hang, Lisa E.

doi:10.6004/jnccn.2022.0020

Cited by 153 publications

(159 citation statements)

References 112 publications

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“…When SJS/TEN is suspected, urgent dermatologic evaluation is necessary and inpatient admission should be considered and ICB as well as other potential culprit medications should be held ( 15 ). Those with widespread mucocutaneous desquamation or life-threatening complications should be admitted to the intensive care or burn unit ( 16 ).…”

Section: True Stevens-johnson Syndrome and Toxic Epidermal Necrolysismentioning

confidence: 99%

“…ICB must be discontinued once true ICB-associated SJS/TEN diagnosis is confirmed. National Comprehensive Cancer Network (NCCN) Guidelines for Management of Immunotherapy-Related Toxicities (version 1.2022) ( 15 ) provide recommendations for SJS/TEN management (without differentiating the treatment for both true SJS/TEN and SJS/TEN-like rashes) with prednisone or methylprednisolone 1–2 mg/kg/day and intravenous immune globulin (IVIg) 1 g/kg/day and/or other immunosuppressive therapies, including etanercept and cyclosporine can be considered for true SJS/TEN ( 15 ).…”

Section: True Stevens-johnson Syndrome and Toxic Epidermal Necrolysismentioning

confidence: 99%

“…Wound care, topical emollients and high-strength topical steroids can be started ( 27 ). NCCN Guidelines for Management of Immunotherapy-Related Toxicities (version 1.2022) for SJS/TEN management (without differentiating the treatment for both true SJS/TEN and SJS/TEN-like rashes) with prednisone or methylprednisolone 1–2 mg/kg/day and IVIg 1 g/kg/day and/or other immunosuppressive therapies, including etanercept and cyclosporine can be considered for true SJS/TEN ( 15 ). While etanercept, cyclosporine, and/or IVIg are preferred for true SJS/TEN, topical and systemic steroids are typically used as first-line for SJS/TEN-like eruptions; use of cyclosporine, IVIg, and/or targeted therapies including etanercept, infliximab, tocilizumab, dupilumab may also be considered ( 27 – 29 ).…”

Section: Stevens-johnson Syndrome and Toxic Epidermal Necrolysis-like...mentioning

confidence: 99%

“…Patients can be given prednisone 0.5–1 mg/kg/day and up to 2 mg/kg/day if there is no improvement. After the rash resolves to grade 1 or 0, prednisone should be tapered over 4–6 weeks and ICB may be re-challenged ( 15 ). As a targeted, steroid-sparing agent, tocilizumab, an anti-IL-6R monoclonal antibody that limits Th17 differentiation and pro-inflammatory response, may be considered for persistent maculopapular rashes ( 32 ).…”

Section: High-grade Maculopapular Rashesmentioning

confidence: 99%

“…Omalizumab has also been shown to relieve pruritus with increased IgE ( 33 ). Per NCCN Guidelines for Management of Immunotherapy-Related Toxicities (version 1.2022), gabapentinoids, aprepitant, and narrow-band UVB phototherapy may also be considered for persistent and severe pruritus ( 15 ).…”

Section: High-grade Maculopapular Rashesmentioning

confidence: 99%

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High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer

Kuo

Markova

2022

Front. Med.

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Immune checkpoint blockade (ICB) improves survival in many types of cancers including melanoma, non-small cell lung, renal cell, breast, and cervical cancers. However, many of these therapies are also associated with high grade dermatologic adverse events (DAEs), including Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), SJS/TEN-like reactions, high grade maculopapular and psoriasiform rashes, autoimmune bullous eruptions, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may limit their tolerability and use. It is important to properly identify and treat DAEs to ICB because these DAEs may be associated with positive anti-tumor response and patients may have limited options for alternative anti-cancer therapeutics. In this review, we describe high grade DAEs to increasingly used ICB agents, which target CTLA-4 and PD-1 or its ligand, PD-L1 and enable the immune system to target cancer cells. We further differentiate life-threatening adverse reactions from mimickers and report cases of serious DAEs which have been recorded in association with ICB through the FDA Adverse Events Reporting System (FAERS), which is an archive of adverse events associated with various drugs and therapeutic biologic products reported voluntarily by consumers and healthcare professionals as well as mandatorily by manufacturers. Lastly, we summarize management recommendations for these adverse events and discuss knowledge and evidence gaps in this area.

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Section: True Stevens-johnson Syndrome and Toxic Epidermal Necrolysismentioning

confidence: 99%

Section: True Stevens-johnson Syndrome and Toxic Epidermal Necrolysismentioning

confidence: 99%

Section: Stevens-johnson Syndrome and Toxic Epidermal Necrolysis-like...mentioning

confidence: 99%

Section: High-grade Maculopapular Rashesmentioning

confidence: 99%

Section: High-grade Maculopapular Rashesmentioning

confidence: 99%

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High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer

Kuo

Markova

2022

Front. Med.

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Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer

Xu,

Jiang,

Pan

et al. 2023

JAMA

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ImportanceGastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy.ObjectiveTo compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100).Design, Setting, and ParticipantsRandomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021.InterventionsPatients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years.Main Outcomes and MeasuresThe primary end point was overall survival time from randomization.ResultsOf the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (&lt;0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P = .002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%).Conclusions and RelevanceAmong patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT03745170

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The “Heater” of “Cold” Tumors–Blocking IL‐6

Pu,

Ma,

Wang

et al. 2024

Advanced Biology

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The resolution of inflammation is not simply the end of the inflammatory response but rather a complex process that involves various cells, inflammatory factors, and specialized proresolving mediators following the occurrence of inflammation. Once inflammation cannot be cleared by the body, malignant tumors may be induced. Among them, IL‐6, as an immunosuppressive factor, activates a variety of signal transduction pathways and induces tumorigenesis. Monitoring IL‐6 can be used for the diagnosis, efficacy evaluation and prognosis of tumor patients. In terms of treatment, improving the efficacy of targeted and immunotherapy remains a major challenge. Blocking IL‐6 and its mediated signaling pathways can regulate the tumor immune microenvironment and enhance immunotherapy responses by activating immune cells. Even transform “cold” tumors that are difficult to respond to immunotherapy into immunogenic “hot” tumors, acting as a “heater” for “cold” tumors, restarting the tumor immune cycle, and reducing immunotherapy‐related toxic reactions and drug resistance. In clinical practice, the combined application of IL‐6 inhibition with targeted therapy and immunotherapy may produce synergistic results. Nevertheless, additional clinical trials are imperative to further validate the safety and efficacy of this therapeutic approach.

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Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology

Cited by 153 publications

References 112 publications

High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer

High Grade Dermatologic Adverse Events Associated With Immune Checkpoint Blockade for Cancer

Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer

The “Heater” of “Cold” Tumors–Blocking IL‐6

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