Friday, 22 Jun 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.

Recommendations

  • 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 .

 

 

 

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

Add new comment

More Like This

NSAID Use Around Conception Increases Miscarriage Risk

A study from the American Journal of Obstetrics & Gynecology analyzed pregnant women from the Kaiser Permanente healthcare system and compared newly pregnant women who took non-steroidal anti-inflammatory drugs or acetaminophen or neither showed that using NSAIDs around conception carried a more than four-fold higher risk of early miscarriage. (Citation source: http://bit.ly/2tqNWN6)

Could Measuring Drug Levels with TNF Treatment Hurt Your Patients?

Our colleagues in gastroenterology measure drug levels with certain biologics used in inflammatory bowel disease in order to increase the dose for optimal benefit if the patient has a low trough level (i.e. targeting drug level).

There have been GI trials with T2T with drug levels but they are not always suggesting that the strategy is superior to usual care. Also, this is really not a common practice in rheumatology.

Methotrexate Update

I was delighted to see that investigators presenting work at EULAR 2018 haven’t lost interest in our old friend methotrexate, with a number of abstracts examining issues of safety, dose and route of administration.

Low incidence of methotrexate induced liver abnormalities

Cancer Therapies Inducing Immune-Related Adverse Events (irAEs)

Recent shifts in the cancer treatment paradigm towards immune therapies has led to wide implementation of the novel immune check point inhibitors (ICI) in the treatment of multiple types of advanced cancer.

While being quite effective in oncology, these checkpoint inhibitors have led to the emergence of a quite unique spectrum of rheumatologic conditions presented under the umbrella of immune-related adverse events (irAEs).

Tobacco Associated Deaths in the USA

JAMA Internal Medicine reports that in the USA, those who smoke cigar, pipe, or cigarette have a significant overall  mortality risk, and a much highers cancer mortality risk compared to nonsmokers.

The National Longitudinal Mortality Study collected baseline survey data from 1985 through 2011 and included 357,420 participants reporting on their use of cigar, pipes, or cigarettes.