Where should bispecific antibodies be positioned in RRMM?

Where should bispecific antibodies be positioned in relapsed and refractory myeloma.

So bispecific T-cell antibodies or T-cell engagers is a very new, exciting kind of category of options or treatments that we have for multiple myeloma. Right now, there's just one product that's approved, FDA approved, and that's teclistamab. It's a BCMA binding bispecific T-cell engager.

And the indication currently is for patients who've had four or more prior lines of therapy.

And our triple class exposed, meaning you've had to have had a drug from the immunomodulatory group. So these would be drugs like lenalidomide or pomalidomide, a drug from a proteasome inhibitor category. So either drugs like bortezomib or carfilzomib or one of the cd38 monoclonal antibodies. So this would be like daratumumab or isatuximab.

So you have to have been exposed to all three of those categories and have had four or more prior lines of therapy in order to get the currently approved FDA teclistamab.

Talvey and Elrexfio received FDA approval in August 2023 for myeloma patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti Cd38 monoclonal antibody.

I think that there's certainly a lot, you know, clinical trials is certainly a huge thing that we encourage patients at any point in their treatment. Any time you need to switch treatment or start a new treatment would be a good time to reassess whether there's a clinical trial available.

And there's certainly a lot of clinical trials that are ongoing looking at bispecific T-cell Engagers.

Whether that is still with BCMA as a target, or there's new targets that we're exploring things like GPRC5D and some of these other newer targets I think are really exciting.

But yeah, for now at least standard of care, you can only get it four or more lines after therapy.

We have we now have bispecific antibodies in myeloma.

The first one approved is teclistamab and there's multiple other bispecific that are being studied and teclistamab targets, BCMA, B-cell maturation antigen.

And BCMA is a really good target. We have CAR-T cells for BCMA. We had an antibody drug conjugate that's not available anymore and now we have teclistamab the bispecific targeting BCMA.

The reason BCMA’s such a good target is because it's really primarily only on myeloma and plasma cells.

We have learned with really effective BCMA targeted therapy. It's on some neurologic cells that can explain some of the neurologic side effects that happen with really potent BCMA targeted therapies.

And so right now teclistamab is approved for patients who've had four prior lines of therapy in the choices and patients who’ve had four prior lines of therapy in a large part are the bispecific antibodies, teclistamab and the car T-cells. Bispecific antibodies, I like to choose to use bispecific antibodies in those patients whose myeloma is progressing somewhat rapidly because we can very quickly initiate bispecific antibody therapy in contrast to what we're able to do with CAR-T cells.

We know, just like almost every other drug that we've studied in myeloma teclistamab and other bispecific antibodies are going to be moved earlier in the course of disease. And there's currently studies in looking at teclistamab as a second line therapy with combinations. As consolidation, there are bispecific antibody studies that are going to look at, could it be use as maintenance therapy, could it be used as initial therapy. We’re even having discussions is can this be used to help prevent myeloma progression in patients with smoldering myeloma?

So just because it's approved right now in greater than four lines of therapy, as we study it more, we're going to learn the optimal place, which will be earlier in the course of disease

Well, I think that we're going to find out now that we have potentially more bispecifics available.

At the moment, we're using them for people who have relapsed after a CAR-T cell or for people who we can't get a CAR-T cell slot for early enough and they need some immediate therapy we're using in those two situations.

I think with more research and more studies, we may in fact be moving the bispecifics much earlier, even as early as front line therapy. I can imagine, a daratumumab, teclistamab, talquetamab induction. I mean, that's far off, but I can imagine something like that. Three shots, minimal toxicity, deep remissions, maybe cure.

Who knows. But I can I can see them moving earlier and earlier and earlier.

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