When are bispecific antibodies and CAR T-cell therapy used for DLBCL, and how might that change in the future?

When are bispecific antibody and Car-T cell therapy used for Dlbcl? And how might that change in the future?

At the present time today, both bispecific glofitamab and epcoritamab have the same indication, which is diffuse large B cell lymphoma having received two lines of therapy?

The first line of therapy is classical immuno chemotherapy; R-CHOP or R-CHP polatuzumab. And the second line depends where the patient had received CAR-T cell have received eventually transplant or have received other kind of second line therapy.

So this is the current, approval by FDA.

But we are working very actively to bring these very active drug earlier in the management of the patient.

And we have already clinical trials that are bringing these bispecific antibody in the first line setting, which means in combination with R-CHOP or R-CHP-polar, these trials are being performed currently. We don't have the result, but it is not unlikely that in 2 or 3 years, bispecific antibodies for certain patients will be part of the first line management.

At the same time, we have also some studies that are being done in patients that are not candidate for CAR-T or before CAR-T that are in vision because of the efficacy of these drugs. There is also a study that has been performed combining bispecific antibody with chemotherapy showing a remarkable efficacy of this combination.

What does the future direction of research for Dlbcl look like?

In diffuse large B-cell lymphoma the goal is to cure patient and cure is better achieved in the first line setting just after the diagnosis with the first treatment. So there are different ways of thinking about that.

The first one is to combine bispecific with classical immuno chemotherapy, which is a treatment received by the vast majority of patients.

We also think that some patients, particularly patients that are very frail with comorbidities or very older patients, may not be good candidate for immuno chemotherapy.

And we just opened a trial by, my colleague Doctor Toker, which administered bispecific with another drug, an antibody drug conjugate initially in the management of the disease in the intent to eventually diminish the immuno chemotherapy, decrease the intensity and duration, and possibly in the future, not having to do it.

And I think this is a great hope for patients who, right now are not good candidate for immuno chemotherapy because of their stages. This is just starting, but other efforts are being done in this area. So that's bringing the first research, first line settings.

The second research that we are participating in and actively involved are combination with other agents.

So this can be, as I mentioned, antibody drug conjugate but other immune stimulating agent.

We do know that bispecific engage T cells and activate T cell. Unfortunatly, Sometimes T cell are not fit or become exhausted. So we are using additional immunological signals to prevent this exhaustion or to increase the fitness of these T cells. Another research that we are doing in some of our trials is investigating, the tumor before the bispecific and during the bispecific treatment to precisely understand the mechanism of action of these bispecific.

What are the interplays between these T cells, the tumor cells and the other cells that are in the milieu in order to find ways to further increase the efficacy of bispecific. But again, three decades ago, the monoclonal antibody anti CD20, rituximab and others have represented a major progress in the treatment of Dlbcl. In the last decades, we have seen CAR-T cell being another tool, and here we are seeing a third tool which probably will generate major advances and will find its pace in the armamentarium that we have. The goal again, is to cure more patients, mostly in the first line. If this doesn't work in the first line, offering them a chance for cure later on in the disease.