[Krista Rubin]

Wow! Thanks for sharing this case Virginia. I too would have suspected hypophysitis with the initial symptoms described. How frightening for this gentleman who probably though he was having a heart attack (myocarditis from the provider perspective)! Was there anything, in hindsight, that may have been an earlier clue to the diagnosis? Or was it due diligence in the ER that ultimately led to diagnosis?

A great example of how ICIs continue to challenge even the most experienced providers!!

[Krista Rubin]

Good question. In thinking about “survivorship issues: that would be specific to an I/O patient, I would include the following- this is just off the top of my head, and a start. I am sure I am missed many components. Would be great if others would add to this….

Management of physical symptoms
* Arthralgias/joint pains
– need for chronic analgesia, safety mobility issues, need for PT
* Neuropathy
– need for chronic analgesia, safety/mobility issues, need for PT, is patient safe to drive?
* Xerostomia-
– oral hygiene, F/U with dental
* Scar management
* Lymphedema
* Physical limitations impacting work
* Other

Psychosocial
* Vitiligo, scar, [body image issues]
* Anxiety
– particularly around restaging scans- “scananxity”
– do they identify with the term “survivor”
* Depression
* Impact on personal relationships
* Impact on work-related relationships

Endocrine
* If hypothyroid–> likely lifelong replacement
* If hypophysitis–> likely lifelong replacement (possibly multiple hormones)
* Adrenal insufficiency
– temporary vs permanent will indicate need (or not) for lifelong replacement
– plans for “sick day” steroid dosing, need for medical bracelet
* Other

If the patient was on long-term steroids for toxicity
* Addressing bone health: calcium supplements, Dexa scan, etc.
* Hyperglycemia/DM
* Other

Family Planning
* Recommendations for pregnancy avoidance, and if so, guidance about how long to wait
* Other

[Krista Rubin]

Thanks Mollie, for that wealth of info.!!

Clearly cost is inhibitory for many (or most). I’m sure with time, this will become a greater issue prompting more and more attention being directed at exploring this issue.

[Krista Rubin]

Totally agree Rajni. The pyrexia can be a HUGE issue.

The FDA has until June 16th to make final decision…however, the rumor mill suggests within a month we may have new options!

[Krista Rubin]

While less chair time is ideal for patients and staff alike, we have not yet made the move to the 4-week dosing. Two reasons:

– We are a bit hesitant to go that amount of time between visits. When and if we do make the transition, most likely we would do so with the “trusted” patients 1st. The ones we feel confident they WILL contact us to report a new or changing symptom.

– More importantly to our group and worth mentioning here is that data from the Checkmate 038 trial (unpublished data- can be provided if you ask BMS for it) demonstrating a higher incidence of Grade 1 and Grade 2 hypersensitivity/ infusion reaction for both nivo monotherapy, and nivo + ipi combination at the 30 minute infusion rate. No high grade reaction, NO deaths.

So- for now, we will make decisions on case-by-case basis. However, it is nice to have options!!

[Krista Rubin]

Given the unknowns with regard to fertility issues and ICIs and targeted therapies; we have been counseling patients about the possibility of sperm/egg harvesting. I have to be honest and say this is a little unsettling to tell patients we “just don’t know”. Sperm banking, technically is relatively low tech; however, egg retrieval is a bigger deal (admittedly I know next to nothing about it). The ramifications of this recommendation, I imagine, could be significant (emotionally, physically) not to mention the costs! As alluded to above, this tends to pertain to the adjuvant setting primarily. In the metastatic setting; that conversation is entirely different.

Couple questions:
1) Does anyone know if insurance will cover costs for fertility (male or female) counseling for patients in the adjuvant setting. Since this is not “antineoplastic chemotherapy” I would fear it would not be covered at all.

#2) Does anyone know of a fertility specialist at their institution (or anywhere else) that may be willing to act as a resource? It would be great to have some experts weight in on this.

#3) What is the responsibility of Pharma in these situations? Can they release data about any post-Rx pregnancy complications or infertility issues s/p Rx on ICI or targeted therapy (post marketing data I would suspect) or data from expanded access trials.

I would appreciate any insight anyone has to offer. These situations are challenging; and I feel like a fish out of water.

[Krista Rubin]

Thanks Kathleen. Nice and concise- great resource.

[Krista Rubin]

Wow- Lisa- thanks for posting this Very important information.
Our group has not yet decided what we are going to do as there are a couple of issues we are planning to discuss as a group. The information you provide Lisa, will need to factor into this as well.

The issues our team felt needed to discussed include:
–> our group has some concern about going 4 weeks between visits. While the schedule is more convenient for patients, it minimizes the chances of “early intervention” which we know is so very important when screening for toxicity.

–> anecdotal experience suggests there may be a higher incidence of infusion reaction at this dose. I have inquired with BMS regarding formal data in his regard. So- PLEASE NOTE- this is ANECDOTAL. But, if indeed true, if is important to consider

Thanks again Lisa- for sharing this info!!

[Krista Rubin]

As of this week, we will be doing what Lisa is doing as well: all nivo over 30 minutes.
We have been administering ipi over 30 minutes for the past couple of years and will continue to do so with ipi + nivo combinations.

[Krista Rubin]

Glad we are all on the same page.
Cost/copay is another to consider. The more competition, the better the prices. So hopefully more on the market means more patients are able to afford what can be astronomical copays in some cases.

I will say, however, my experience with the investigational BRAF/MEKi (encorafenib + binimetinib) has been quite positive. My understanding is this combo has not seen the pyrexia as the others are. IF indeed true, this would be a notable & important difference and may very much sway usage.

[Krista Rubin]

Great question:
We have been taking this on a case-by-case basis. Though IIIA patients have a favorable prognosis, there are some patients that have a more worrisome feature than the “average IIIA”. For those patients, a detailed risk/benefit discussion is essential, and the patient would be made aware of the data (not including IIIA).

[Krista Rubin]

I totally agree! Pyrexia can be a huge challenge, notably when it is recurrent or resistant to corticosteroids.

[Krista Rubin]

Mollie- Has such a delay led to a change in strategy for management?

[Krista Rubin]

Rajni- you bring up two important points:

– Asymptomatic elevations of amylase and lipase may or may not be clinically significant. These labs, if drawn, must be interpreted in context; and as Lisa states, “blanket” guidelines may results in unnecessary dose holds, or worse yet, unnecessary discontinuation.

– Thanks for pointing out that colitis does not always mean diarrhea! This can be tricky for providers less experienced with the GI effects.

[Krista Rubin]

Thanks!!

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