Tuesday, 20 Mar 2018

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: https://buff.ly/2CQia03)

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 www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .




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

Add new comment

More Like This

Repeat Malignancy Unlikely with Biologic Therapy

Research from the Danish biologics registry shows that the use of a biologic in patients with a history of a primary cancer does not increase the risk of a second malignant neoplasm (SMN) or mortality in rheumatoid arthritis (RA) patients.

They analyzed 15,286 RA patients in the DANBIO Register between 2000–2011 and found 1678 with a primary cancer.  The majority (1203) did not use biologics after. 

Opportunistic Infections in RA Rare with Biologics

The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis has studied nearly 20,000 patients and observed that there is no substantially different risk of opportunistic infections between different biologics. 

Biologics in Pregnancy: Are They Safe?

Exposure to biologic therapies among women with autoimmune diseases was not associated with increased risks of preterm delivery or having small for gestational age babies, a population-based Canadian study found.

DSB – Safety Updates & Drug Shortages – March 2018

This edition of RheumNow's Drug Safey Bulletin includes drug safety news, FDA updates, FDA safety labeling changes and reported drug shortages. 

Steroid Use During Rheumatoid Pregnancies

Pregnant women (n=254) with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study  and who were taking oral glucocorticoids were studied.