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Multiple Myeloma Therapeutic agent Darzalex interfering with testing


ElinF

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4 hours ago, Mabel Adams said:

We have a patient who got his first dose on 3/17/16 but who had a negative antibody screen on 3/31 and 4/13.  On 4/26 he now has a pos screen in gel and a saline tube screen is about 1+ at 37 but barely positive at AHG.  We have sent the sample out for DTT workup.  With his frequent transfusions we may want to get some DTT so we can do the workup ourselves.

Update: the reference lab says that they picked up rouleaux at 37 so maybe that is why that reaction was stronger than at AHG.  We got no rouleaux in his reverse type so didn't think that was what we had at 37.

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We had a presentation 3 weeks ago from the manufacturer at a local BB conference.  They indicated that the positive Ab Screen can show up within the first day and positive DAT can persist 6 months or more post treatment.  They are recommending phenotyping the patients prior to starting DARA therapy and using DTT treated cells for screening and transfusing K negative units to patients who are K neg.

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  • 5 months later...

I currently have 2 patients on the therapy and am trying to get a handle on frequency of ref lab workups after transfusion.  Our first patient has been transfused.  at that time we sent a sample to our ref lab for a workup to confirm that no allo-antibodies were present.  We transfused Rh, K, FY, and JK matched blood. We do not have DTT in-house.  Suggestions on frequency of workups - after each transfusion?  Thanks!

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On 10/25/2016 at 3:44 AM, KKidd said:

I currently have 2 patients on the therapy and am trying to get a handle on frequency of ref lab workups after transfusion.  Our first patient has been transfused.  at that time we sent a sample to our ref lab for a workup to confirm that no allo-antibodies were present.  We transfused Rh, K, FY, and JK matched blood. We do not have DTT in-house.  Suggestions on frequency of workups - after each transfusion?  Thanks!

I work in a reference lab and consensus of opinion here is that you need to resolve reactivity in pretransfusion testing regardless of transfusing phenotype matched blood.   If I was in the hospital, these patients would get treated like any other patient who is transfused; a pretransfusion workup each time they present if the last draw is outside the 3 day window.  Just because ID’ed reactivity is associated with Darzalex the first time, doesn’t mean something else can’t develop later on.  Transfusing phenotype matched blood does not guarantee the patient won’t form a clinically significant antibody to a low incidence antigen or an antigen that isn’t tested for, like Dombrock.  

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7 hours ago, dragonlady97213 said:

I work in a reference lab and consensus of opinion here is that you need to resolve reactivity in pretransfusion testing regardless of transfusing phenotype matched blood.   If I was in the hospital, these patients would get treated like any other patient who is transfused; a pretransfusion workup each time they present if the last draw is outside the 3 day window.  Just because ID’ed reactivity is associated with Darzalex the first time, doesn’t mean something else can’t develop later on.  Transfusing phenotype matched blood does not guarantee the patient won’t form a clinically significant antibody to a low incidence antigen or an antigen that isn’t tested for, like Dombrock.  

I could not agree more.

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I've been thinking about how we would know if these patients made an antibody to an antigen destroyed by DTT.  I guess it would be by them having a transfusion reaction.  Once we are convinced they are destroying transfused cells but their testing with DTT treated cells is negative, how do we figure out what they have?  I understand that eluates will contain the anti-CD38 so that won't really help unless there is a big difference in strength of reactions.  I guess reaction strength could be a clue in plasma testing as well (although both of those will help more if the antibody is to a lower frequency antigen--Dombrock or Kpa, Jsa etc.).  How about testing against 2 or 3 O cord cells?  If they all react, it should be an antibody to one of the high incidence antigens.  If none react, it is more likely directed at a low incidence antigen.  Is this accurate?

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Next question.  I am trying to decide on a policy of whether to do full genotyping or just K typing when we get their pre-treatment specimen.  So far, most of the patients we have on the drug are not needing any transfusions (we still have fewer than 10).  The genotyping is fairly expensive.  If we don't manage to validate DTT treatment in-house, we could have to transfuse emergency patients while waiting for the results to come back from the reference lab.  Then it would be good to have their genotype so we could select phenotype matched units.  But that's not too likely to happen. It is also not too likely that they will have unidentified antibodies in those emergencies. The risk isn't really much more than for uncrossmatched blood; it's just that the transfusion might be needed a little less emergently than a trauma, but they can't wait a day or 2 for the results. It seems like big hospitals are genotyping and some others are just K typing.  What criteria are places using to decide?  Age of patient?  Transfusion history? Presence of other antibodies?  Am I worrying too much about the cost of genotyping?

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On 10/29/2016 at 11:05 PM, Mabel Adams said:

I understand that eluates will contain the anti-CD38 so that won't really help unless there is a big difference in strength of reactions.

Since it has been reported that workers are unable to remove anti-CD38 by adsorption, I suspect that one would be unable to elute said antibody, rather similar to "HTLA" antibodies. An eluate could be free of anti-CD38 and therefore be testable, however, there are hundreds of reports of nonreactive eluates in patients with obvious hemolytic and/or serological transfusion reactions.

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On 10/29/2016 at 11:18 PM, Mabel Adams said:

I am trying to decide on a policy of whether to do full genotyping or just K typing when we get their pre-treatment specimen.  So far, most of the patients we have on the drug are not needing any transfusions (we still have fewer than 10).

Since your patients are NOT getting regular transfusions, I would hesitate to get full genotypes. If they switch over to being regularly transfused, it might be worth reconsidering, but you may paint yourself into a corner and find it necessary to "honor" the other DTT-sensitive antigens like Yt and Do. See DargonLady's comments above.

A K typing can be easily performed using monoclonal antisera, even after the first dose of drug and if the DAT is positive.

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6 hours ago, exlimey said:

Since it has been reported that workers are unable to remove anti-CD38 by adsorption, I suspect that one would be unable to elute said antibody, rather similar to "HTLA" antibodies. An eluate could be free of anti-CD38 and therefore be testable, however, there are hundreds of reports of nonreactive eluates in patients with obvious hemolytic and/or serological transfusion reactions.

I read a research paper in Transfusion on this drug that mentioned eluates being panreactive on these patients (at least the one they studied). http://onlinelibrary.wiley.com/doi/10.1111/trf.13069/full

"An RBC eluate was prepared from a DARA-treated patient sample (Patient 4, Table 1). The eluate was panreactive on RBC panels. Flow cytometry confirmed that the eluate contained binding activity to CD38+ HL60 cells but not to CD38– controls (Fig. 3C). Binding to CD38+ HL60 cells was specifically inhibited by the addition of anti-DARA idiotype (Figs. 3C and 3D), confirming the presence of DARA in the patient sample."

Does anyone have more information on eluates now that more patients have been tested?

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  • 11 months later...

For those of you doing antibody screens on DTT-treated cells, what phases are you including?  We don't usually do IS on screens so won't do that, but we are debating reading at the 37 degree phase vs. just doing IAT only screens.  We would be testing treated cells by a saline method with a 30 minute incubation.  We are getting molecular antigen typing done on the patients for whom we get pre-treatment specimens.  Our usual testing method is gel but not for the DTT-treated cells.

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Mabel, I read on another thread from a couple of people at the reference lab that they were able to get negative antibody screens in tube with LISS.  I tried that on one of our patients (we only have 2 so far) that had a positive screen in gel and was sent out for DTT treatment with no antibodies found,  and the tube screen was negative.  We did not read at 37.  I had gotten a pre-treatment specimen and antigen typed it for all anti-sera we carry (Fy, Jk, K, S, C, c, E, e).  If you do a LISS screen and it's negative, you don't have to give phenotype-matched products since nothing was destroyed.  You don't do that with regular patients, right?  I even emailed our reference lab, since technically these patients would be eligible for EXM with no history of an antibody, but I think I'll stick with IS XM.

So, post-treatment screen in gel, if positive, screen in tube, if negative, do IS XM.

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We follow pos gel screens in these patients with saline screens and have found some negative.  Our standard saline screen includes a 37C phase but we are building a new DTT screen test in the computer and are trying to decide if it should include the 37C phase.  Our reference lab had said that they don't do 37C on DTT treated cells so we were building it as AHG only but now we have learned that they do 37C with untreated cells for these cases (because they do numerous panels and other testing as part of their standard workup rather than just a DTT screen as we would do).  I see from our user group that some are using PEG but we haven't validated that.  How many of you are using PEG for testing DTT treated cells?

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