February 07, 2018
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Survey: Fewer than 30% of oncologists ‘very comfortable’ treating severe immune-related adverse events

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Kerry Lynn Reynolds

Fewer than 30% of attending oncologists reported feeling very comfortable managing patients admitted to the hospital with severe immune-related adverse events following treatment with immune checkpoint inhibitors, according to a survey presented at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Nearly half of the physicians surveyed said patients with severe immune-related colitis, hepatitis, thyroiditis, hypopituitarism, pneumonitis, and central nervous system and renal toxicities should be managed by a special service.

“This suggests there are members of the oncology community who do not feel prepared to manage these cases, which calls for additional education, innovative care models and detailed guidelines,” Kerry Lynn Reynolds, MD, instructor of medicine at Massachusetts General Hospital, told HemOnc Today.

Reynolds noted that the survey was conducted prior to the release of guidelines from Society for Immunotherapy of Cancer and European Society for Medical Oncology.

Checkpoint inhibitors targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the programmed death 1 receptor (PD-1) and its ligand (PD-L1) have become standards of care for an increasing number of indications, including metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, urothelial cell carcinoma, and squamous cell carcinoma of the head and neck.

However, as HemOnc Today previously reported, toxicities from combination immunotherapy can range from skin rashes, mucositis and diarrhea to colitis, sepsis, hypothyroidism, hyperthyroidism, pneumonitis, myocarditis, arrhythmia, type 1 diabetes and hypophysitis, all of which can occur within weeks after initiation.

“The use of immune checkpoint inhibitors is expanding year by year and the number of inpatients with severe immunotherapy-related adverse events rose by threefold from 2011 to 2016 (OR = 3.07; P < .01),” Reynolds said. “Patients are admitted with a variety of presentations affecting different organ systems — including gastrointestinal, pulmonary, endocrine, neuro and cardiac — highlighting the critical need for disease-specific services in the hospital and a need to be familiar with management of these myriad conditions.”

Between February 2011 and June 2017, researchers collected data on patients with advanced malignancy who experienced a suspected immune-related adverse event that required hospital admission. Two reviewers — including one subspecialist — comprehensively reviewed each case. In addition, researchers surveyed oncologists at Massachusetts General Hospital regarding their confidence in managing patients with immune-related adverse events.

Over a span of 6 years, 343 hospitalizations occurred for suspected immune-related adverse events. Of those, 65% (n = 223) required treatment with immunosuppression or discontinuation of therapy.

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Readmission rate was 61.7% for any reason and 25% for another immune-related adverse event. Patients had a mean length of hospital stay of 6.3 days (range, 1-31). The inpatient mortality rate was 8%.

The most commonly reported immune-related adverse events were enterocolitis (43.9%), pulmonary (16%), hepatic (15%), neurologic (8.9%), endocrinopathies (7.1%), rheumatologic (4%), dermatologic (3%), cardiovascular (3%), renal (1.8%) and allergy (1.3%).

In their survey of 26 oncologists at Massachusetts General Hospital, Reynolds and colleagues reported low rates of oncologists felt very comfortable managing various toxicities with consultants and outpatient colleagues, including:

  • 23.5% for colitis (52.9% somewhat comfortable);
  • 23.5% for hepatitis (52.9% somewhat comfortable);
  • 29.4% for thyroiditis (35.3% somewhat comfortable);
  • 23.5% for pneumonitis (52.9% somewhat comfortable); and
  • 23.5% for CNS toxicity (35.3% somewhat comfortable).

Additionally, 48% of oncologists surveyed said complications from immune-related adverse events should be managed by a different service.

“This patient population is readmitted for immune-related adverse events 25% of the time, and readmitted for any cause 69% of the time, which indicates they are a cohort that has a high level of health care utilization,” Reynolds said. “The potentially devastating outcomes from immune-related adverse events requires that we prepare providers and patients for the wave of hospital admissions by developing a coordinated multidisciplinary team-based approach.”

Translational research is needed to identify biomarkers associated with immune-related adverse events and develop strategies to treat those events before they become severe, according to Reynolds. – by Chuck Gormley

 

Disclosures: The authors report no relevant financial disclosures.