Friday, 22 Mar 2019

You are here

ASCO/NCCN Guidelines for Checkpoint Inhibitor Immune-Related Adverse Events

New guidelines have been developed by the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) on how to assess and manage of immune checkpoint inhibitor side effects that are often autoimmune in nature.

Checkpoint inhibitors have been developed as means to "reinvigorate an exhausted immune response" seen in cancer, says Dr. Len Calabrese of the Cleveland Clinic. (Citation source:

Immunotherapy with immune checkpoint inhibitors has revolutionized the treatment of many different types of cancer, making remission a realistic goal. These agents include inhbitors of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways (ipilimumab; nivolumab pembrolizumab, and atezolizumab). The most common side effects with these drugs are rash, diarrhea, hypothyroidism and fatigue.

Unfortunately, they may also given rise to immune-related adverse events (IRAEs), manifest as autoimmune or inflammatory disorders.  There have been hundreds of reports of these immune-related adverse events (irAEs), manifesting as rheumatoid arthritis, psoriatic arthritis, psoriasis, polymyalgia rheumatica, colitis, autoimmune hypophysitis, inflammatory arthritis, spondyloarthritis, Sicca syndrome, myositis, myocarditis, or rhabdomyolysis. 

ASCO and NCNN convened a multidisciplinary, multi-organizational panel of experts (oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy) to develop a clinical practice guideline based on a systematic literature review and informal consensus voting.

While they found 204 eligible publications on IRAEs (most of which were case series and case reports), there was a lack of high-quality evidence and thus, most of these recommendations are based on expert consensus.


  • Management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities.
  • ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less.  Corticosteroids may be administered.
  • Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d).
  • Corticosteroids should be tapered over the course of at least 4 to 6 weeks.
  • Some refractory cases may require infliximab or other immunosuppressive therapy.
  • With grade 4 toxicities, permanent discontinuation of ICPis is recommended, with the exception of endocrinopathies that have been controlled by hormone replacement.
  • Additional information is available at and .




The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

Best of 2018: The Safety of Paternal Exposure to DMARDs and Biologics

Pregnancy and drug safety is a complex issue, often with limited information about maternal drug exposure on the offspring. Greater uncertainty exists when considering whether paternal exposure may also influence fetal outcomes.

A systematic review examined the effect of disease modifying anti-rheumatic drugs (DMARDs) on male fertility and if peri-conception (within 3 months) paternal exposure was detrimental to fetal outcomes.

Best of 2018: Hydroxychloroquine Being Over-Dosed with New Guidelines?

Hydroxychloroquine retinopathy prevention guidelines have revised from ideal body weight-based dosing to actual body weight-based dosing; the question remains whether these have been adopted in clinical practice. A database of nearly 21,000 new HCQ users from a UK general population database studied HCQ dosing and use between 2007 and 2016. Specifically they examined whether users were subjected to excess HCQ dosing per ophthalmology guidelines (defined by exceeding 6.5 mg/kg of IBW and 5.0 mg/kg of ABW).

CDC Top 15 Most Common Opioid Overdose Drugs

The Dec. 12 issue of the National Vital Statistics Reports from the U.S. Centers for Disease Control and Prevention reports that the most commonly abused drugs causing drug overdose deaths (between 2011-2016) include fentanyl, heroin, oxycodone, and cocaine.

Trazodone High Risk of Falls and Fractures

The CMAJ (Canadian Medical Association Journal) has reported that trazadone use in the elderly may be associated with a risk of falls and major fractures. 

Using claims data from ICES, researchers compared 6588 seniors given trazadone to 2875 receiving another atypical antipsychotic.

Musculoskeletal Events with Statin Use

Analysis of the FDA Adverse Event Reporting System data examined the association between statins' musculoskeletal adverse events (MAEs).

Review of the data shows that atorvastatin and rosuvastatin (with strong low‐density lipoprotein cholesterol‐lowering effects) had a higher risk and a faster onset of MAEs when compared with simvastatin.

They could not detect whether concomitant drugs shifted the onset timing of MAEs.