ONCAlert | Upfront Therapy for mRCC

Available CD38 Antibodies for Multiple Myeloma

Targeted Oncology
Published Online:1:00 PM, Fri January 10, 2020

Adriana Rossi, MD: Of the new agents targeting CD38, I think the one that is coming closest to a clinical use will be isatuximab, which is a monoclonal antibody also targeting CD38, with a slightly different mechanism of action profile. In addition to targeting the tumor cells it has been shown to affect NK [natural killer] cells and effector cells. And so similar to daratumumab, but with a slightly different epitope, and again, a slightly different toxicity profile. It will be interesting to see as daratumumab is likely to be approved in the subcutaneous administration, how the 2 will compare and how clinical practice will then embrace using 1 before the other.

I think we’re certainly waiting on data to show sequencing. One of the biggest questions we get, especially from community physicians, now that we have so many tools in our armamentarium, is: is there a purposeful reason for which we should use 1 before the other, or is there something in patient selection that would help us find the right patient in whom to use 1 agent over the other?

I think it is exciting. There are other modes of action targeting CD38. Both antibodies that are used with radiotherapy, and now as we are developing more and more immunotherapies, there are CAR T [chimeric antigen receptor T-cell] agents that are targeting CD38. I think it will be interesting not only using the target but using it in different modalities. And as far as mechanisms of resistance, loss of antigen is something we worry about, but one of the things we’ve seen is that addition of 1 drug to another could actually rescue efficacy.

Transcript edited for clarity.

Adriana Rossi, MD: Of the new agents targeting CD38, I think the one that is coming closest to a clinical use will be isatuximab, which is a monoclonal antibody also targeting CD38, with a slightly different mechanism of action profile. In addition to targeting the tumor cells it has been shown to affect NK [natural killer] cells and effector cells. And so similar to daratumumab, but with a slightly different epitope, and again, a slightly different toxicity profile. It will be interesting to see as daratumumab is likely to be approved in the subcutaneous administration, how the 2 will compare and how clinical practice will then embrace using 1 before the other.

I think we’re certainly waiting on data to show sequencing. One of the biggest questions we get, especially from community physicians, now that we have so many tools in our armamentarium, is: is there a purposeful reason for which we should use 1 before the other, or is there something in patient selection that would help us find the right patient in whom to use 1 agent over the other?

I think it is exciting. There are other modes of action targeting CD38. Both antibodies that are used with radiotherapy, and now as we are developing more and more immunotherapies, there are CAR T [chimeric antigen receptor T-cell] agents that are targeting CD38. I think it will be interesting not only using the target but using it in different modalities. And as far as mechanisms of resistance, loss of antigen is something we worry about, but one of the things we’ve seen is that addition of 1 drug to another could actually rescue efficacy.

Transcript edited for clarity.
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