Nivolumab dilution

[Anonymous]

Hello everyone. In my institution nivo protocol is still 3mg/kg diluted with sodium chloride 0.9%, 60min IV infusion. I’ve got two questions:
1. Patient A, weight 90kg – 270mg nivo dose. Is there any benefit of diluting 270mg of nivo in 100ml sodium chloride 0.9% IV versus smaller 50ml IV bag of sodium chloride 0.9%?
2. After the infusion of nivo is finished, is there any difference between flushing the IV line with 50ml sodium chloride vs 25ml? Thanks in advance for clarification.

[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

[Anonymous]

Thank you Kathy for this great reply. It’s very helpful. I’ll definitely bring up the topic of the new dosing regimen as per the article posted.

I’ve got one more question regarding dosing of nivo that you could possibly clarify. If “patient’s A” weight (currently at 90kg) goes down at some point by let’s say 2kg would that warrant change of dosing straight away i.e. lowering it by 6g to 264mg total or would the change in weight need to be more substantial in order to justify change of current dose? Thank you.

[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

[Author]

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