[Mandi Murph]

Wow, very interesting & challenging case. I have had 1 patient with a similar experience quite sometime ago but we had treated him with short term steroids. As I thought about this case, it conjures up results that some of my patients share after seeing a Naturopath or Functional medicine doc. Stools studies are fairly common place within the integrative care setting. We all are aware that so much of our immunity is related to the gut micro biome. An alarming rate of Americans have large quantities of candida in their GI tracts causing all kinds of disruption to body function & regulation, especially over long periods of time. With that said, I wonder if Bri, your patient may have been heavily colonized with candida at baseline and the ICI set them up for an opportunistic infection. Just a thought.
Our center is doing gut micro biome research studies with stool samples in the lab setting, nothing yet moving into the clinical setting, stay tuned.

[Mandi Murph]

Thanks for sharing your experiences, we don’t yet have full resolution, but the pt has returned to her normal life style and eating/ drinking normally & finds this little bit of residual tolerable. Fortunately, this was in an adjuvant setting, Krista glad to hear that your pt who was unresectable still received benefit off therapy. Sjogren’s can be a challenge but there are management strategies, noentheless still a challenge.

[Mandi Murph]

HI Lisa,

Happy New Year!
Great inquiry regarding transplant pts & the use of ICI’s. Our practice has a handful of transplant pts, we have tended to shy away from pd-1 inhibitiors due to some case studies of organ transplant rejection. Pts have in these cases been treated with a CTLA-4 inhibitor. However, some of the more recent case studies have a mix of pts receiving pd-1 or combination therapies and tolerating these therapies without rejection. We have not yet had a pt with met SCC related to immune suppression secondary to transplant, we have only treated standard of care pts with cemiplimab. More case studies and discussion are certainly needed to compile more risk vs benefit info.

Great topic!

Kathy

[Mandi Murph]

HI All,

A quick update on my patient with mucositis, she received infliximab ab on 12/27, I received a fu call on 12/28 & she was already experiencing regression of swelling, sensitivity and pain. I will provided an additional update to provide time to sx resolution.

Happy Healthy New Year to All!

Cheers,
Kathy

[Mandi Murph]

HI Julie,

if there is a 10% weight loss or gain a weight based dosing can be evaluated for and adjustment. However, if we have a combination or a flip dose situation ( ipi 1mg/kg & nivo 3mg/kg) we may adjust accordingly to a clinical situation of weight loss or gain. My institution and practitioners tend to stick with the weight based dosing though.
I am so excited to hear that you are considering taking back to your institution some of the updated dosing recommendations, please know that we continue to be here as a source of support for you, your colleagues & patients. Thank you again for your engagement & inquiries. Happy Healthy Thanksgiving!

All the Best,

Kathy

[Mandi Murph]

HI Julia,

Thank you for your inquiries!

Question # 1 RE dilutions for Nivo

Your pt who is 90 kg receiving 270mg Nivo (3mg/kg) q2Wks over 60 min for Melanoma
PER the PI, Max recommended total volume of Nivo in dilution should not exceed 160ml per infusion
Your pts vial requirements are as follows:
Nivolumab 240mg/24ml vial = 24ml, + 40mg/4ml vial (minus 10mg or 1 ml) = 27ml or 270mg of actual Nivolumab undiluted
27ml + 50ml of NS= 77 ml infusion
27ml + 100ml of NS= 127 ml infusion
Either dilution is acceptable as they do not exceed the maximum recommended volume of 160ml
Infusion time recommendations are 30 or 60 mins, for your lower dilution volume and more concentrated dosing, considering adhering to a 60 min infusion time as pd-1 inhibitors do carry ~10% infusion reaction rate.

My center for example for a 480mg IV q 4 wk dosing is using the following:
40mg/4ml vial= 48 ml + 110 NS
total volume 158ml over 30 min
We typically provide a higher volume for the infusion and a lower volume flush for the line.

Question #2 re IV line flush:
Standard IV lines carry between a 20 ml & 25ml priming volume ( noted on packaging) , so a 25 to 50 ml flush- either is acceptable to clear drug from the line

My personal bias is a higher diluent fluid volume and a lower flush volume.

I would like to note that the 240mg IV q 2 week & 480mg Q 4 weeks are approved and part of the Prescriber indications for melanoma in the adjuvant setting & maintance post combination therapy induction (in the US, Canada & EU).
Flat dose was approved through pharmacokinetic analyses taken from phase III trials across tumor types and established flat dose exposure relationships and clinical safety. I have included a current article noted below discussing flat dosing. The consensus is for the same efficacy & safety, there is also cost efficiency as well as time flexibility for patients and staff. Your center may want to investigate the possible benefits of expanding it’s dosing regimen choices for nivolumab. Nurses are great change agents and advocates, I hope that you may consider bringing back to your center some updated evidence to support that discussion as well as the evidence that supports the expanded dosing regimens.

Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer
G V Long S S Tykodi J G Schneider C Garbe G Gravis M Rashford S Agrawal E Grigoryeva A Bello A Roy S
Annals of Oncology, mdy408, https://doi.org/10.1093/annonc/mdy408
Published: 12 September 2018

Thank you again for your inquiry, I hope this was helpful and answered your questions.
Best Regards,

Kathy

[Mandi Murph]

Thanks you Suzanne, this is a great reference to share!

[Mandi Murph]

HI Morgan,

In my practice I have had patients experience fevers of up to 105, that is not the norm though, most patients experienced fevers up to 101-103. We try to prevent such high fevers by having patients notify the treating office at the onset of any adverse events.
However, the newer braf/ mek combination encorafenib & binimetinib during clinical trials demonstrated and 18% rate of pyrexia, lower incidence than other braf mek combinations. This may be a good alterantive to another combination, if pyrexia is a dose or treatment limiting side effect.
Thank you for your input and questions, Morgan.

Regards,
Kathy

[Mandi Murph]

My pt with sensorial hearing loss due to localized labrythitis non met related, is going for tubes in her ears to allow direct instillation of corticosteroid drops, if this is not helpful or if the process is taking a very long recovery, a cochlear implant is on the table for discussion. I can’t emphasize how increadibly rare this is but these are some of the cases that as we go we are learing and sharing.
I so appreciate that Suzanne you shared that you have had patients have tubes placed and it was helpful, I was able to take that anecdote & clinical experience back to my team & my patient that other patients have been through this.

[Mandi Murph]

I have found the NCCN app very helpful when on the go, if I need to look up the irAE management guidelines. I work with one of the docs who authored the asco paper and we had a very rare late toxictiy evolve in a patient and I was able to pull up the guidelines in the the exam room onmy phone through the app to check the management strategy. The cool thing about the app too is that all of the guidelines have the most up to date version as the app is updated, so the most current info is at your finger tips.

[Mandi Murph]

Dear Morgan,
So glad that you are finding the forum valuable and of interest. Please do share & we welcome questions so please feel free to join in as there is an expert nurse overseeing this Q & A forum everyday.

thanks again for stopping by!

Warm Regards,
Kathy

[Mandi Murph]

This past week I have had 2 more patients on Braf/Mek- tovi’s experience febrile toxicities preceeded by several days of mild anorexia. While the drugs were placed on hold, some of the symptoms proceeded to get worse or persist about 3-5 days later, I am attributing this to the long half life. Febrile work ups have been negative, no other clinical sx of infection. Low dose steroids have been most effective for these cases.
Next step plan is to get to back to baseline & dose reduce & restart.
Any similar experiences?

[Mandi Murph]

Any one else transition patients from tag/mek or zelb/cobi over to braf/mek-tovi?
So far the paients that we transitioned are all doing quite well. there are 2 patients who have had stroing GI toxicities & flu like sx within a month of starting tx who required drug holiday & dose reduction after 2 attempts to restart full dose & they are doing better on the reduced dose.

[Mandi Murph]

I have had several patients with ICI related sensorial hearing loss due to nerve inflammation & irritation, steroids were helpful but it was the combination of steroids & time that reversed this irAE.

However, I have 1 paient who has been off ici therapy due to pod transitioned to braf/mek therapy for > 6months and developed acute neurological sx about 12 weeks post ICI therapy. Sx consisted of vertigo, headache, vision changes with no brain metastases. she has been on & off steroids for months. She has been seen by ENT & has recently been receiving steroid injections into her ears for labrynthitis.Her most recent mri confirmed this & no presence of brain metastases.

[Mandi Murph]

There are several patients in our practice who have either experienced a mild infusion reaction or post treatment fatigue and myalgia, we are premedicating these patients with dexamethasone or solumedrol IV and they have no furhter issues during or post infusion. 2 other patients have had some occassional GI upset resolvable with a medrol dose pak post tx.

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