Treatment of R/R DLBCL: CD19-Targeted Monoclonal Antibodies


Ali McBride, PharmD, MS, BCPS, BCOP: Tafasitamab has actually come to light for the treatment of relapsed/refractory diffuse large B-cell lymphoma with the emergence of the L-MIND study, where we have seen this therapy start to come into play. Hopefully, we’ll see it approved here shortly with the FDA. Tafasitamab is a novel therapy. It’s a CD19-based treatment therapy. We have seen its emergence here rather quickly into the clinical trial and also in the combination with the L-MIND study too.

It’s a novel drug discussion across the board. Tafasitamab is actually an Fc-engineered humanized CD19 monoclonal antibody that has 2 mechanisms of action. It has ADCC [antibody-dependent cell-mediated cytotoxicity] and also ADCP [antibody-dependent cellular phagocytosis]. These are mechanisms for dependent-based complement activation and phagocytic activation for MOA [mechanism of action]. Therefore, it potentiates cell death in these cases and induces apoptosis of those targeted cells with that backbone on tafasitamab.

We have been talking about ADCC for a while with several other drugs, mainly in the CD28-based discussion pathway. But now with tafasitamab utilizing a CD19-based expression pathway for activation, we have a very large target activation of B cells versus CD20. Also, we address a novel payload mechanism for activation utilizing the ADCC and also ADCP. These combinations and also the expression for CD19 on these B cells allow for potential increased cytotoxicity against these tumor cells.

Again, we are looking at the mechanism and also addressing combinations here as well. We hope to express a better outcome based on the current studies and also current evolution of this therapy into diffuse large B-cell lymphoma and also other non-Hodgkin lymphoma as well.

With the tafasitamab we really touched on the fact about access, and this is going to be an important discussion with tafasitamab versus CAR [chimeric antigen receptor] T-cell therapy. With the evolution of CAR T, you have to have CAR T at certain centers, so these are called centers of excellence. They also have to be allowed to administer CAR T to those patients in the setting. These are actually mostly larger facilities. They make a distance away from community-based practice settings.

From that standpoint, not everyone may have local access CAR T therapy. That may be a limitation along the lines of treatment. In addition, you may have patients who are transplant ineligible, so they can’t undergo a CAR T based process and therefore will not be eligible as well. We have 2 unfortunate determinants that may not allow for patients to get CAR T in an easy manner. In addition, when we’re taking a look at CAR T in itself, there may be other preclusions as well as cost, which we talked about too.

When we’re taking a look at community-based practices or other practices, they may not have access to CAR T. We know that tafasitamab will come in really moving this setting and the paradigm along for transplant-ineligible patients, taking that picture very quickly. We expect a quick uptake for treatment with tafasitamab in the settings because they can be seen at their community oncologist and receive therapy. We’ve done this before with many other therapies as well.

In this setting, we also have a lower incidence of infusion-related reactions, so therefore making it safer for patients to tolerate this drug therapy with the antibody. That means that patients have better access and also quicker treatment time to get that therapy on board. That evolution in the CAR T setting versus the tafasitamab setting really promotes utilization of tafasitamab for those transplant-ineligible patients.

When it comes to CAR T, if patients are transplant eligible, we may see some sequencing discussions happen in their future. Do you do tafasitamab maybe as a bridge? We’ll touch upon this a little later, but even in the L-MIND study, there was 1 patient who after receiving tafasitamab had actually undergone CAR T and therefore was treated and actually had a continued response.

There may be some sequencing pieces here alluding to the fact that tafasitamab not only might be used in the transplant-ineligible setting, because you can’t actually utilize CAR T for those patients, but it also potentially may be providing the means to get that patient into a CR [complete response] setting, and thus allow for CAR T as well, so there’s some potential there in addition to it. I look forward to how this slowly evolves into the current treatment pathways and paradigms for relapsed/refractory diffuse large B-cell lymphoma.

Transcript edited for clarity.

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