Anti-CD38 therapy

[Bb_in_the_rain 98]

On 12/24/2015 at 8:28 PM, Mabel Adams said:

Does anyone know what would happen if someone mistook this situation for a warm auto and did a PEG autoadsorption on the sample?  Or maybe an alloadsorption?  Can this antibody be adsorbed out?

This antibody will not be adsorbed out since the dose is very high relative to CD38 expression on RBC. 

[Bb_in_the_rain 98]

On 9/14/2015 at 7:05 AM, John Eggington said:

It's odd; nothing in the literature suggest that the antigen is destroyed, only that the (white) cells that express it are destroyed. A few theories as to the nature of the destruction are postulated.

I am guessing red cells doesnt get destroyed because CD38 expression on red cells are very low? 

[Bb_in_the_rain 98]

On 11/18/2015 at 4:20 PM, Mabel Adams said:

And now it is FDA approved in the US.

 

Multiple myeloma drug from J&J receives FDA approval
Johnson & Johnson has won FDA approval for the use of Darzalex, or daratumumab, in multiple myeloma patients who have received at least three lines of standard therapies. The decision was backed by data from two trials, including a 42-patient study showing that tumors were completely or partially reduced in 36% of patients who took the drug. Reuters (11/16)

 

 

Do all patients taking the drug show the effects outlined on this thread or do some have a weaker or undetectable effect?  I need to have a discussion with our oncologists (among other things).

I think it depends on the method used. ECHO solid phase has shown to have weak to negative reactions with screen cells and panel cells from what I have seen so far. But non-the-less they were positive screens (weakly reactive but not all cells were reactive) that we had to work up an antibody identification. By tube method. it is reactive with PeG, LISS and saline IAT. 

Edited December 30, 2015 by dothandar

[kirkaw 58]

This therapy has come to my hospital. Thankfully, our oncologist gave me a heads up. Apparently, the drug manufacturer is strongly suggesting that prescribing doctors communicate with their transfusion services. They even provide cards for the docs to give the patients, that can be presented, should the patient go to a different hospital (I'm envisioning something like a card from the Red Cross that details what antibodies a patient has).

Anywho....since I do not routinely stock DTT, and haven't used it in 20 years, my 'frontline' strategy has been to get a complete phenotype on the patient before he gets his 1st daratumumab treatment this afternoon. I am simultaneously trying to find a supplier and pricing for DTT (anyone, anyone?) to determine if this is something we want to undertake or do we want to send these specimens to our reference lab every time.

[Mabel Adams 1,023]

What are you reporting for XMs? Least incompatible in AHG? Compatible by IS?

[Rita 10]

Would anyone be able to share their procedure for the treatment of red cells with DTT?  We are looking into whether or not we should add this procedure to our Transfusion Service, and I'm just wondering how involved it is.  Thanks!

[Mabel Adams 1,023]

Hemobioscience sent out information on their new DTT product that had instructions for using it for various purposes.  If you haven't had any answer yet, try contacting them.

[noelrbrown 27]

Hemo bioscience is selling ready to use DTT ( frozen), see our web site for details.  

[applejw1 27]

PEG differential adsorption does not adsorb out anti-CD38 and I have seen the reactivity mistaken for a warm autoantibody - looks just like it with exception that autocontrol was either negative or very weakly reactive with a negative DAT.  0.2M DTT treatment of reagent and donor red cells does remove anti-CD38 reactivity - have done it for 2 patients.  Have only been able to phenotype one patient before patient had received red cell transfusions - still haven't had to transfuse that patient (of course).

Heme Bioscience has sent out emails about having 0.2M DTT (frozen) available for purchase - $50 for a 2ml vial.

[CMFreeman 1]

I'm working at the MD Anderson blood bank here in Houston now and we see this pretty regularly - at least 10/week easily. Probably because we treat a lot of myeloma patients that have been through multiple standard regimens elsewhere. Its in our standard instructions now to look at drug history for Dara if we see the patient has multiple myeloma. 

Usual pattern after a recent dose is for screens and panels to have no reactivity at 37, micro pos or 1+ at AHG, and about the same with ficin treated cells.  A/C is Usually negative (I'd estimate maybe 75% of the time), but occasionally will be micro Pos at AHG, same strength DAT, and elution will be negative.  Crossmatches usually show micro pos incompatibility, so we end up doing a lot of pathologist approvals for "least incompatible units".  We use the Bioarray instrument for patient genotyping on these, so we can do antigen matching in future if the pathologist decides its warranted. 

We are starting parallel testing with DTT treated panels soon so we wont be essentially transfusing blind anymore.  The sales pitch does make it sound simple, but experience will tell.

 

 

Edited April 30, 2016 by CMFreeman
clarity

[Mabel Adams 1,023]

We have had only one patient to test who is on this drug.  His screen remained negative until he had had, I think 3 doses, then it was positive a couple of times and now it has been negative again the past 2 times.  We are testing him about once a week for transfusions.  Today's specimen has a note that says his last dose was 5/6.  Is anyone else seeing patients stay negative or return to negative while being treated?  He also had a lot of rouleaux the times he was positive which made teasing apart which was showing up where kind of tricky.  The other local patients on the drug haven't needed transfusions.

 

[swede 43]

On ‎5‎/‎25‎/‎2016 at 8:40 PM, Mabel Adams said:

We have had only one patient to test who is on this drug.  His screen remained negative until he had had, I think 3 doses, then it was positive a couple of times and now it has been negative again the past 2 times.  We are testing him about once a week for transfusions.  Today's specimen has a note that says his last dose was 5/6.  Is anyone else seeing patients stay negative or return to negative while being treated?  He also had a lot of rouleaux the times he was positive which made teasing apart which was showing up where kind of tricky.  The other local patients on the drug haven't needed transfusions.

 

We currently have 2 patients on this drug.  One of them has only been transfused once in the past couple of months, and her screen was negative. The other has been transfused multiple times. She was negative for 3 rounds, then 1+ positive in GEL.  Currently she is negative again.......

[Mabel Adams 1,023]

New wrinkle:  We are trying to validate the use of DTT to treat cells.  We thought all was going fine until we decided to include testing the treated cells to make sure that the Fyb antigen wasn't destroyed in the treatment process (we chose Fyb because Duffy antigens are a bit more fragile than most and we don't always use the whole vial of antisera before it expires as we do anti-Fya so didn't mind wasting some).  We tested 3 DTT treated reagent cells.  The K antigen was destroyed as expected.  Two cells appeared to be double dose Fyb and 1 was single-dose (I suppose one might have been from a hemizygous donor but there were no other antigenic clues).  One of the double-dose cells and the single-dose cell no longer reacted with the anti-Fyb.  The other double-dose cell reacted 3+.  We have repeated treatment and various bits of the testing and have contacted vendors of pretty much everything we used to get some advice. I think we can rule out a problem with that lot of anti-Fyb as a new lot behaved the same.  At least one investigation is pending by the supplier of the pre-diluted DTT.  Has anyone seen something like this?

 

[Mabel Adams 1,023]

Reporting back.  We have spent a lot of time chasing this and still need to talk to the reagent red cell manufacturer.  The latest test showed some DTT treated single-dose Fyb reagent cells not reacting with our human source anti-Fyb but cells from multiple units/patients who were known to be Fyb single dose did react just fine.  Generally, double-dose Fyb pos reagent cells maintain their antigen strength through DTT treatment and that is what is always represented on screen cells we would be using.  I assume the manufacturers avoid using donors likely to be hemizygous for Fy antigens as part of screen cell sets.  I'll let you know if we learn more.

[WisKnow 6]

On April 8, 2016 at 6:26 AM, noelrbrown said:

Hemo bioscience is selling ready to use DTT ( frozen), see our web site for details.  

Is this the 0.2M DTT that we use to treat reagent red cells in HTLA or anti-CD38 cases? 

[noelrbrown 27]

yes it is, Hemo bio sells it frozen ready to use and you can buy it powdered from other vendors.   Noel