[Krista Rubin]

There is much in the literature regarding this issue and for those not familiar with the literature, it is worth reviewing. Bottomline- underlying autoimmune disease should NOT automatically be a contraindication to I/O therapy. However, as I am sure your practice is similar- there is no absolute right or wrong answer.

In our practice, decision to recommend I/O therapy to someone with underlying autoimmune dz (such as RA, colitis, psoriasis, etc) will vary depending on multiple factors to be considered based on each INDIVIDUAL patient. For example:
-is the underlying autoimmune issue well controlled?
-are they on immunosuppressive medications currently? what line of therapy (1st line, 5th line…)
-is there a specialist involved that would be willing to co-manage with oncology?
-is the patient reliable to report any new or worsening symptoms? do they have family/caregiver support?
-do they have additional comorbidities that would further increase risk
-Importantly- what is tumor burden- and have they had prior melanoma therapies?

Really, the decision comes down to is risk/benefit. If a patient has significant tumor burden and prognosis is poor- and they WILL die from their melanoma without intervention, then the benefits of trying I/O would seem to outweigh risks. Then there is the flip side to that as well.

We often see patients in consultation regarding safety of I/O therapy in such a patient. If the primary oncologist does not have enough of a comfort level with making such a decision, we will often weight in, and we are happy to co-manage or provide consultations regarding symptom management. There is not right answer here, as I am sure you know.

What I hate to hear about, is a patient being denied treatment to potentially life-prolonging or life-saving therapy due to lack of comfort or knowledge by a provider.

I would be very interested to hear how others address.

PS- my answer above relates to metastatic diasease. The adjuvant setting is a whole different discussion!!

[Krista Rubin]

Thanks Lisa. The patient has lesions that are ideal to inject…but the ocular herpes history makes me nervous. Other options are being explored.

[Krista Rubin]

I agree with Lisa. However, I find that many of the PCPs feel uncomfortable managing some issues and encourage the patient to see their oncology team. In the few instances I have time/opportunity to call the PCP directly to provide just a quick “heads up” – it is so appreciated by the PCP and then they feel more comfortable reaching out to us with any issues. Even with shared EHRs- a phone call really does go a long way as often they have to dig in the notes to figure out what a pt is receiving.

[Krista Rubin]

Curious to hear how others would handle:

Would your practice consider TVEC for a patient with a HISTORY OF recurrent herpetic infections (including ocular) that required daily suppression?

[Krista Rubin]

I believe Kathy’s point that education occurs not only BEFORE a patient starts treatment, but DURING, as well as ONGOING education is so critical. We all know that patients hear about 20% of what they are informed…so repeat education is key.

When I see patients, I also try to include “practical” information as well.
For example, in the winter here in New England- it snows! So- including information about what they should do if they do not feel they can safely get to our facility, or, if a snow storm shuts the road down. I also include information about drinking alcohol, what happens if they have vacation plans (do they need to cancel), about whether or not they can drink alcohol. Safe sexual practices are also discussed if appropriate.

We all know just how much there is to cover with cancer treatment education and clearly this can not be provided in one session. Having a variety of educational materials available is ideal to reach ALL types of learners: verbal information, written, and, if possible, various media related educational tools. Videos, DVDs, on-line, etc.

If anyone has examples of tools, or resources they use, we would love to hear about them!!! The more resources we can provide to our patients (and to each other) – the better.

[Krista Rubin]

I have not; though admittedly our experience with T-Vec is fairly limited at this time.

[Krista Rubin]

Hi Lisa-
This is a great question and until recently, the concept of cardiotoxicity was under appreciated.

As you know, ICIs are associated with numerous toxicities related to underlying immune dysfunction as a result of the mechanism of action. So, it should be no surprise that cardiac toxicity could be seen. Though rare, cardiotoxicity is something that must be on the radar of providers caring for patients receiving these agents as fatal cases of myocarditis and pericarditis have been seen.

Diagnosis can be difficult. Fatigue and edema can be early symptoms, but notably, typical cardiac workup can be negative!! CPK and troponins should be checked in anyone suspected of cardiotoxicity. If elevated, this should not be ignored. It is important to note that in the literature, as well as in our clinic, we have seen patients undergo cardiac cath for suspected cardiotoxicity, and be told they had a negative test (for ischemia). The inflammation often occurs in and around the heart, and not necessarily in coronary arteries; that is why CPK and troponins are so important.

Cardiac ECHO or MUGA scan can show decreased EF, or LV hypertrophy. You don’t want to miss those changes, however subtle. Cardiac biopsy is often necessary for diagnosis.

Nurses can improve patient safety with identification of patients whom might be at greater risk including those with pre-existing cardiac issues, patients with cardiac metastases, and patients whom have received prior cardiotoxic cancer therapies (including targeted therapies) including radiation in the area of the heart.

Recognition of symptoms and prompt initiation of steroids and consultation with cardiology to-manage are key to decreasing morbidity and mortality.

[Krista Rubin]

Great question Lisa!

Very exciting data released in Spain this past September at ESMO regarding what is known as the COMBI-AD trial. This was an adjuvant trial for patients with stage III BRAF-mutant melanoma; it was a double-blind trial randomizing 870 patients 1:1 to either dabrafenib + trametinib versus double placebo. Patients received treatment X 1 year.

Bottom line: The combination of dabrafenib (Tafinlar) + trametinib (Mekinist) reduced the risk of relapse or death by 53% compared with placebo. AMAZING!

Toxicity to some degree was seen in almost all of participants (97%). Of those, 41% was grade 3/4 compared to 88% and 14% with placebo, respectively. About 1/4 of stoped treatment as a result of toxicity (compared to 3% on placebo). The higher toxicity rate in this trial compared use of d+t in Stage IV trials is thought to be related to the fact that the majority of the participants did not develop progressive disease, therefore they received the full year of treatment. The longer patients receive treatment, the more likely they are to develop toxicity.

With regard to the adjuvant nivolumab, known as CheckMate 238- more exciting data! This was a randomized double-blind phase III trial comparing adjuvant nivolumab versus ipilimumab (remember this is now a standard, FDA approved adjuvant treatment). There were 906 patients with stages IIIB, IIIC, and IV resected melanoma]. Results showed a significant improvement in RFS (66.4%) compared to ipilimumab (52.7%). In fact, the trial was stopped early when it became clear that nivo was superior to ipi!

In addition, there was much less toxicity seen with nivo compared to ipi (14% vs 46% respectively); only 10% of patients receiving nivo stopped treatment due to toxicity, while 43% receiving ipi had to stop.

Both studies have been published in the NEJM.

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