Collaboration essential for management of immunotherapy toxicities

NEW YORK — Immunotherapy-related toxicities can be identified through careful monitoring and physicians should collaborate with other specialties to determine the best treatment, according to a presenter at HemOnc Today New York.

Immune-related adverse events can occur in most organs in the body.

“Of course, there are certain organs that are more susceptible to these adverse events,” Shirish M. Gadgeel, MD, professor of medical oncology at University of Michigan, said during his presentation. “The potential mechanism of these adverse events commonly is believed to be T-cell infiltration, but there are instances, such as colitis, that seem to be related to interleukin 17.”

Patients on immunotherapy should be monitored closely for treatment-related adverse events. Gadgeel recommended seeing patients during the first four to six cycles of treatment and to educate patients about the possible concerns with therapy.

“It is very important that you make patients aware of the unique nature of these adverse events and not to discount any symptom that they have because they could be related to these drugs,” Gadgeel said. “Also, make your colleagues, particularly physicians from other specialties, aware that these drugs cause a variety of side effects in a variety of organs.”

Thyroid levels should be taken at baseline and during the first four cycles, and periodically after, to monitor for hyperthyroidism and hypothyroidism, among the most common immunotherapy-related adverse events.

Most adverse events occur within the first 6 months; however, some can be delayed.

“Timing is important to be aware of, especially in terms of pneumonitis. It tends to occur within 3 months. So, if someone is on a PD-1 inhibitor and about 1 year later there is evidence of respiratory distress, it may be some other reason, but of course pneumonitis is possible. So, being aware of timelines of these adverse events is relevant,” Gadgeel said.

Clinicians should refer to the guidelines for specific treatment recommendations. However, generally treatment can be categorized for mild, moderate or severe adverse events.

Grade 1 toxicities can by treated with symptom management and therapy can usually continue.

Depending on the patient, clinicians should treat grade 2 toxicities by adjusting immune checkpoint inhibitor therapy. Steroids can be considered for these patients.

When grade 3 or higher toxicities are present, guidelines recommend discontinuing therapy and immediately starting steroids and possibly other immune suppressants.

Clinicians should be aggressive with steroids, starting IV steroids quickly if severe toxicities are suspected, Gadgeel said. Additionally, pneumocystis pneumonia and gastrointestinal prophylaxis should be started immediately.

Patients should also be slowly tapered off steroids, in some cases over a period of about 6 weeks. Adverse events can flare up if steroids are not tapered slowly.

“If you suspect an immune-related adverse event, don’t hesitate to start immune suppression because, the earlier you start, the better you’re going to be able to control the immune-related adverse event,” Gadgeel said.

Some common adverse events include rash, diarrhea, hypothyroidism and pneumonitis.

With thyroid toxicities, patients can be treated with steroids and hormone replacement. This adverse event is unique in that, if patients are well managed, immunotherapy can be restarted.

“Unlike other toxicities when they are very severe, you are to avoid immune checkpoint inhibitors, subsequently that might not be true when it comes to thyroid function,” Gadgeel said.

For diarrhea and suspected colitis, clinicians should rule out Clostridium difficile, but generally steroids should be started, and a gastrointestinal consult should be conducted.

Skin rash is more common with CTLA-4 therapy than with PD-L therapy. Sun exposure can also increase risk for rash. Most minor rashes can be treated topically, but more severe symptoms should be treated with steroids. Gadgeel also recommended obtaining a dermatology consult as early as possible.

“This is true of any of these side effects. Don’t hesitate to get a consultant relevant to that side effect involved as early as possible, Gadgeel said. “They can make suggestions regarding the management of these side effects and they make it much easier on you and your patients.” – by Cassie Homer

Reference:

Gadgeel SM. Side effects of immunotherapy agents: How to manage. Presented at: HemOnc Today New York; March 8-10, 2018; New York.

Disclosures: Gadgeel reports consultant roles with Ariad/Takeda, Roche/Genentech, AstraZeneca and AbbVie.