NCCN Guidelines® Insights: Management of Immunotherapy-Related Toxicities, Version 2.2024.

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell-engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

Onco-Primary Care of Patients Receiving Immune Checkpoint Inhibitors.

Primary clinicians foster long-term relationships with patients and play key roles in the treatment journey for patients with cancer. Primary clinicians are important members of the multidisciplinary team and are central in coordinating and providing supportive care. The use of immune checkpoint inhibitors in adjuvant/neoadjuvant treatments and metastatic disease requires an awareness of their long-term survival benefits and immune-related adverse events (irAEs).

FDG PET/CT Imaging 1 Week after a Single Dose of Pembrolizumab Predicts Treatment Response in Patients with Advanced Melanoma.

Purpose: Immunologic response to anti-programmed cell death protein 1 (PD-1) therapy can occur rapidly with T-cell responses detectable in as little as one week. Given that activated immune cells are FDG avid, we hypothesized that an early FDG PET/CT obtained approximately 1 week after starting pembrolizumab could be used to visualize a metabolic flare (MF), with increased tumor FDG activity due to infiltration by activated immune cells, or a metabolic response (MR), due to tumor cell death, that would predict response.

Patients And Methods: Nineteen patients with advanced melanoma scheduled to receive pembrolizumab were prospectively enrolled.

Advanced Practice Provider Model for Urgent Oncology Care.

Inherent to the cancer disease trajectory are heightened risks for a plethora of comorbid diagnoses. As the treatment landscape for oncology therapeutics continues to rapidly advance, patients are living longer and potentially experiencing more symptoms requiring rapid assessment. Prompt assessment and intervention for cancer or cancer treatment-related symptoms is imperative to achieve patient comfort and obtain the best overall patient outcomes.

PD-1 directed immunotherapy alters Tfh and humoral immune responses to seasonal influenza vaccine.

Anti-programmed death-1 (anti-PD-1) immunotherapy reinvigorates CD8 T cell responses in patients with cancer but PD-1 is also expressed by other immune cells, including follicular helper CD4 T cells (Tfh) which are involved in germinal centre responses. Little is known, however, about the effects of anti-PD-1 immunotherapy on noncancer immune responses in humans. To investigate this question, we examined the impact of anti-PD-1 immunotherapy on the Tfh-B cell axis responding to unrelated viral antigens.

Automated Text-Based Symptom Monitoring With Rapid Clinician Triage for Patients With Cancer and Suspected or Confirmed COVID-19.

Purpose: Patients with cancer are at greater risk of developing severe symptoms from COVID-19 than the general population. We developed and tested an automated text-based remote symptom-monitoring program to facilitate early detection of worsening symptoms and rapid assessment for patients with cancer and suspected or confirmed COVID-19.

Methods: We conducted a feasibility study of Cancer COVID Watch, an automated COVID-19 symptom-monitoring program with oncology nurse practitioner (NP)-led triage among patients with cancer between April 23 and June 30, 2020.

NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020.

The NCCN Guidelines for Management of Immunotherapy-Related Toxicities provide interdisciplinary guidance on the management of immune-related adverse events (irAEs) resulting from cancer immunotherapy. These NCCN Guidelines Insights describe symptoms that may be caused by an irAE and should trigger further investigation, and summarize the NCCN Management of Immunotherapy-Related Toxicities Panel discussions for the 2020 update to the guidelines regarding immune checkpoint inhibitor-related diarrhea/colitis and cardiovascular irAEs.

A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma.

Immunologic responses to anti-PD-1 therapy in melanoma patients occur rapidly with pharmacodynamic T cell responses detectable in blood by 3 weeks. It is unclear, however, whether these early blood-based observations translate to the tumor microenvironment. We conducted a study of neoadjuvant/adjuvant anti-PD-1 therapy in stage III/IV melanoma.

Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response.

Tumour cells evade immune surveillance by upregulating the surface expression of programmed death-ligand 1 (PD-L1), which interacts with programmed death-1 (PD-1) receptor on T cells to elicit the immune checkpoint response. Anti-PD-1 antibodies have shown remarkable promise in treating tumours, including metastatic melanoma. However, the patient response rate is low.

Timing of Onset of Adverse Cutaneous Reactions Associated With Programmed Cell Death Protein 1 Inhibitor Therapy.

Importance: An increasing number of cutaneous adverse reactions resulting from use of programmed cell death protein 1 (PD-1) inhibitors have been described, but with relatively little focus to date on the timing of these reactions.

Objective: To determine the timing of cutaneous drug reactions after initiation of PD-1 inhibitor therapy.

Design, Setting, And Participants: This retrospective observational study included patients referred to an academic dermatology clinic by an oncologist from January 1, 2014, through February 28, 2018, with at least 1 skin biopsy specimen of a skin reaction associated with PD-1 inhibitor use.

Lupus-like cutaneous reaction following pembrolizumab: An immune-related adverse event associated with anti-PD-1 therapy.

PD-1 (programmed cell death-1) inhibitors, used to treat metastatic melanoma and other malignancies, are associated with development of immune-related adverse events in the skin. Such reactions include morbilliform eruptions, vitiligo, alopecia areata and bullous pemphigoid. In this report, we describe a patient who developed a lupus-like cutaneous reaction in the setting of pembrolizumab therapy for metastatic melanoma, adding to the spectrum of reactions which may be observed in association with PD-1 inhibitor therapy.

PD-1 Inhibitor Therapy: Consensus Statement From the Faculty of the Melanoma Nursing Initiative on Managing Adverse Events .

Background: Programmed cell death protein 1 (PD-1) inhibitor therapies are now a standard treatment for advanced melanoma and other tumor types. The immune-related adverse events (irAEs) associated with PD-1 inhibitor therapy are drastically different from the AEs associated with chemotherapy. Because these irAEs reflect immune system activation rather than side effects of therapy, nurses should be cognizant of the range of organ systems potentially affected as well as likely clinical presentations.

T-cell invigoration to tumour burden ratio associated with anti-PD-1 response.

Despite the success of monotherapies based on blockade of programmed cell death 1 (PD-1) in human melanoma, most patients do not experience durable clinical benefit. Pre-existing T-cell infiltration and/or the presence of PD-L1 in tumours may be used as indicators of clinical response; however, blood-based profiling to understand the mechanisms of PD-1 blockade has not been widely explored. Here we use immune profiling of peripheral blood from patients with stage IV melanoma before and after treatment with the PD-1-targeting antibody pembrolizumab and identify pharmacodynamic changes in circulating exhausted-phenotype CD8 T cells (T cells).

Acute visual loss after ipilimumab treatment for metastatic melanoma.

Background: Ipilimumab, a humanized CLTA-4 antibody is a standard therapy in the treatment of advanced melanoma. While ipilimumab provides an overall survival benefit to patients, it can be associated with immune related adverse events (IrAEs).

Case Presentation: Here we describe a patient treated with ipilimumab who experienced known IrAEs, including hypophysitis, as well as a profound vision loss due to optic neuritis.

Improving the Safety of Oral Chemotherapy at an Academic Medical Center.

Purpose: Over the last decade, the use of oral chemotherapy (OC) for the treatment of cancer has dramatically increased. Despite their route of administration, OCs pose many of the same risks as intravenous agents. In this quality improvement project, we sought to examine our current process for the prescription of OC at the Abramson Cancer Center of the University of Pennsylvania and to improve on its safety.

What you are missing could matter: a rare, complex BRAF mutation affecting codons 599, 600, and 601 uncovered by next generation sequencing.

Testing for somatic mutations in tumor samples is becoming standard practice in a number of tumor types where targeted therapies are available. Since clinical care is dependent on the identification of the presence or absence of specific mutations, it is important that these mutations be identified consistently and accurately. Here we identify in a patient with metastatic melanoma a novel, complex mutation involving BRAF c.

Diverse cutaneous side effects associated with BRAF inhibitor therapy: a clinicopathologic study.

Background: Vemurafenib, a novel selective small molecule inhibitor of BRAF, has recently been shown to be effective in the treatment of melanomas harboring the BRAF V600E mutation. Similar to the broad-spectrum RAF inhibitor sorafenib, vemurafenib induces development of squamous cell carcinomas and keratoacanthomas as a side effect of therapy.

Objective: We sought to detail additional cutaneous adverse effects of vemurafenib and a similar BRAF inhibitor, dabrafenib.

Side effects in melanoma patients receiving adjuvant interferon alfa-2b therapy: a nurse's perspective.

Purpose: The aim of this review was to examine the toxicity profile of adjuvant interferon (IFN) alfa-2b in melanoma patients from a nursing perspective and to summarize practical information to guide the effective management of common IFN toxicities to improve patient comfort.

Methods: This is a narrative summary of both research and review articles identified by searching PubMed, National Cancer Institute, and American Cancer Society websites. It also assesses recognized guidelines on the management of adjuvant IFN toxicity relevant to nurses who are caring for patients receiving adjuvant IFN therapy.

IL-8 and cathepsin B as melanoma serum biomarkers.

Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. Melanoma serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies of serum biomarkers have often been hampered by the serum interference that causes false readouts in immunological tests.