CR 241: Itching for Opdivo

I've been taking nivolumab (Opdivo) for almost exactly a year. From time to time I've noticed that a rash forms a day or two after my infusion. I am aware that a rash is one of the most common side effects from Opdivo. The FDA safety information for Opdivo advises, "Immune-mediated rash can occur with Opdivo treatment. Monitor patients for rash." FDA's detailed prescribing information for Opdivo states on page 8 that a rash occurs in greater than 20% of patients. According to UpToDate,

Dermatologic toxicity is the most common immune-related adverse event (irAE) associated with checkpoint inhibitors (table 1). Approximately 50 percent of patients treated with ipilimumab will experience rash and/or pruritus, and approximately 30 to 40 percent of those treated with nivolumab or pembrolizumab will have dermatologic complications.

For me, the most common location of rash was on my calves, the back of my scalp, and around the base of my neck. In the past it has come and gone and not been much of an irritant. After my last infusion last week, however, I had a much more significant rash develop on my calves. It circled both lower legs from just above the ankle to a few inches below the knee, and comprised of hundreds of tiny red prickles that itched like crazy. After trying to control it with a Benadryl gel, on Tuesday I sent a midnight email to Dr. Hahn:

Since my last infusion on Feb. 11, I have developed a localized rash on both calves. I would categorize it as a grade 1 rash, being a localized maculopapular faintly erythematous rash with pruritis. I have been applying a Benadryl gel as a topical analgesic, but am wondering if I should apply a corticosteroid. Looking in my medicine cabinet, I see 3 different creams: lidocaine and prilocaine cream, 2.5/2.5%; clidamycin phosphate benzoyl peroxide gel, 1.2/5%; and fluticasone propianate cream, .05%.  Are any of those suitable? Or should I get a scrip for something else? Please advise on whether I should be seen before my next a scheduled infusion on Feb. 25. Many thanks for your ongoing excellent care.

The next morning, Dr. Hahn responded:

Normally, I would usually start with simple over the counter hydrocortisone 1% or 2% cream.  The fluticasone is stronger than the hydrocortisone and dermatologists usually reserve that for more severe cases.

I promptly went out and got some hydrocortisone, and it seems to be helping manage the rash. I also started researching why Opdivo can cause dermatologic toxicity, and what should be done about it. A post on Cure Today from July 2015 describes how to manage rashes caused by immunotherapy drugs such as Opdivo. A 2014 article entitled "Managing the Side Effects of Novel Cancer Immunotheraputics" described the function of Opdivo as sometimes contributing to dermatologic toxicity: 

PD-1 is expressed by T lymphocytes and, upon interaction with its ligands (PD-L1 or PD-L2), functions as a co-inhibitory receptor that dampens T-cell activation, thereby negatively regulating the immune response. Treatment with monoclonal antibodies that disrupt the interaction between PD-1 and PD-L1 results in significant antitumor activity.

A 2015 article published by ASCO entitled "Toxicities of Immunotherapy for the Practitioner" explained:

The basis for the majority of these adverse events is a hyperactivated T-cell response with reactivity directed against normal tissue, resulting in the generation of high levels of CD4 T-helper cell cytokines or increased migration of cytolytic CD8 T cells within normal tissues. The T-cell immune response is not tissue specific and may reflect a diffuse expansion of the T-cell repertoire that induces cross-reactivity with normal tissue, effectively breaking tolerance that is active with cytokines, vaccines, and checkpoint protein inhibitors and passive in the case of adoptive cell therapy.

The question for Dr. Hahn next week is what if anything we should do now that my skin has started protesting a little louder about Opdivo. I suspect that we'll continue on with the doses, dealing with the rash as long as it does not rise to grade 3 or 4. If this is the most significant side effect of Opdivo, then it's full speed ahead. It's a hundred times better than either of my chemotherapy regimens. If it gets to the point where all my hair falls out (again) and I feel like I'm climbing out of a hole each time I get an infusion, then maybe I'll start reconsidering it. But so far, so good.