Imlifidase is licensed by SMC for desensitisation treatment of highly sensitised adult kidney transplant patients unlikely to be transplanted under the available kidney allocation system including prioritisation programmes for highly sensitised patients.
- Candidate patients are decided at the MDT to be both immunologically (as per SMC criteria) and clinically eligible to received the drug.
- Patient require re-transplant vaccinations for pneumococcus, meningococcus (tetravalent and sero-group B), influenza and SARS-CoV-2.
- Patients are given the Edinburgh patient information leaflet (attached below) and counselled in clinic/Near Me.
- If patients agree, then HLA specificities are de-listed as per local policy and discussion between H&I and transplant teams. At this point pharmacy will be contacted to order in the drug and de-listing should not occur until the drug is on site, as it may take some days.
- Patient will require enhanced HLA antibody screening while waiting for an offer – every 4 weeks.
- If an offer is received for the patient, the H&I scientist will liaise with the duty/on-call transplant team and indicate that this patient is on the imlifidase pathway.
- The patient should have a 10ml clotted sample sent to H&I on arrival for HLA antibody testing. In addition, a 20ml EDTA tube is required for later crossmatch. The antibody test may not need to be repeated if done within the past 4 weeks but we still require the sample for retrospective testing.
- The results of the HLA antibody testing will determine if imlifidase is needed or not. It may be appropriate to transplant without imlifidase if the transplant is deemed lower risk e.g. historic antibodies only or low level current antibodies. This decision will need to be made by the duty/on-call transplant team (nephrology & surgery) in discussion with the H&I scientist.
- If a non-imlifidase transplant is possible from assessment of the HLA antibody data, then the wet crossmatch using donor peripheral blood samples will be performed to further assess the immunological risk of this approach.
- When a patient receives an offer for an imlifidase enabled transplant, the on-call co-ordinator will notify pharmacy at the earliest opportunity that imlifidase is required. The usual cascade system for contacting pharmacy will be used:
- Monday-Friday 8:30-17:00 via Transplant Pharmacist (bleep 2294).
- Weekend – within opening hours (Sat 9:00-15:00, Sun 10:00-14:30) via dispensary ext. 22911 or 22912.
- Outwith pharmacy opening hours – on-call pharmacist contacted via switchboard.
- Once the organ is inspected by the transplant surgeon and deemed transplantable, imlifidase may be administered if deemed necessary.
- A repeat 5ml clotted sample should be sent 4 hours post-imlifidase. At 6hours post-imlifidase, repeat 2 x 5ml clotted samples – for HLA antibodies and wet cross-match using spleen/lymph nodes – should be sent. *
- The decision to transplant will be based on the 6 hour DSA and crossmatch tests. The 4 hour sample is for local audit/learning. It may be that retrospectively we see that a 4 hour sample will suffice. Until then, decision making will be based on the 6 hour sample.
- If the 6 hour HLA antibody sample is negative, which would be expected, the transplant can go ahead.
- If this sample remains significantly DSA positive, it is a contra-indication to transplantation. In Scotland, the drug is licensed for one repeat dose if necessary. It is predicted that this is very unlikely to occur so it should be discussed with H&I and a second clinical opinion in the unit before proceeding to a repeat dose. *
- If the cross-match remains positive despite no HLA antibodies being present, this is likely due to a non-IgG antibody and the transplant could likely go ahead after a discussion with the duty/on-call transplant team.
- After transplantation, HLA antibody samples should be sent at the following intervals; day +4, +7, +10, +14, weekly thereafter for 6 weeks or as clinically indicated in response to graft dysfunction. Following this if patient’s function is stable, samples will be tested at 3 months, 6 months and annually thereafter.
- For patients outwith Lothian, communication between the home team and an Edinburgh transplant nephrologist should occur once weekly for at least the first 6 weeks. This arrangement should be clarified at discharge and could be the duty transplant nephrologist or one of the nephrologists who do the regular outreach MDTs.
*Currently a second dose will not be possible even if indicated as stock is ordered on a case by case basis so we will be in a similar situation to the rest of the UK.
Note: a group and save must be sent to SNBTS on admission to the ward. This is already standard for all transplant patients. The additional importance for imlifidase patients is that SNBTS want to ensure that full red cell antigen testing is performed as imlifidase could interfere with this assessment if the patient subsequently needs a red cell transfusion.
Treatment Protocol for Imlifidase in highly sensitised kidney transplant patients
Imlifidase will not be administered until the patient is deemed suitable, medically and immunologically, and the organ has been inspected by the transplant surgeon.
- Pre-medication: IV chlorpheniramine 10mg and IV Methylprednisolone 500mg IV to prevent infusion reactions which may occur.
- Imlifidase 0.25mg/kg IV to be reconstituted as per manufacturer advice/IV guide (see below).
- IV Methylprednisolone 500mg IV & again 24 hours after first dose (as per standard protocol).
- Day 2-4, IV Methylprednisolone 125mg daily.
- Tacrolimus & MMF as per standard protocol. Aim tacrolimus trough of 8-10 for 3 months. MMF 1g BD even if aged > 60 years.
- Day 4: Alemtuzumab (Campath) 30mg s/c
- Day 5: Prednisolone oral 75mg
- Day 6: Prednisolone oral 50mg
- Day 7: Rituximab 375mg/m2
- Day 7 – day 28: Prednisolone oral 20mg daily
Infection prophylaxis:
- Cotrimoxazole 480mg od for 6 months.
- Valganciclovir as per standard protocol (i.e. 6 months): CMV prophylaxis even if CMV-IgG D-/R- cases is suggested due to HSV & VZV risk as well as primary CMV infection. We already do this for ATG treated patients
- Pre-transplant vaccinations: This should include pneumococcal, meningococcal (tetravalent and sero-group B), Influenza and SARS-CoV-2 vaccines.
- Anti-fungal and TB prophylaxis: not routine.
- Antibiotic for 4 weeks: UK guidelines say for local preference; local discussion with ID team recommends that this is not needed and cotrimoxazole would suffice.
Preparation of Imlifidase as per IV guide:
- Calculate the number of vials required.
- Reconstitute each 11mg vial with 1.2mL water for injections, gently directing the water to the wall of the vial and not the powder.
- Gently swirl the vial for at least 30 seconds until the powder is completely dissolved. Do not shake, to avoid foaming.
- The reconstituted solution contains 10mg in 1mL (11mg in 1.1mL). 11mg can be withdrawn from each vial.
- Withdraw the dose required and add slowly to 50mL sodium chloride 0.9% bag. Note: the solution should be clear and colourless. Do not use if discoloured or contains particles.
- Invert the infusion bag several times to mix thoroughly.
- Do not use if the solution is discoloured or contains particles.
- Record the brand name, batch number and expiry date from each vial used in the patient’s case notes or drug chart. (For hospitals with electronic prescribing and administration systems follow local policies).
- IV infusion: Give over 15 minutes using infusion pump via a 0.2micron in-line (low protein binding, non-pyrogenic) filter. Protect the infusion bag from light.
Note: Imlifidase can be prescribed on Hepma. It should be documented on VitalData in the ‘Peri-Transplant’ screen, induction section – add ‘Other’ and free text imlifidase/rituximab/alemtuzumab.
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Paul Phelan and David Turner Feb 2024