What are the common side effects of bispecific therapy and how are they managed?

What are the common side effects of bispecific antibody therapy and how are they managed?

Because bispecific activate the immune system and engage T-cell to kill the tumor cell. There is a couple of immune reaction.

The main immune reaction is called the cytokine release syndrome. What happens there? When these T cells are activated and proliferate, they release molecules in the bloodstream and around which I called cytokines, which helps them to proliferate, but which also create a reaction in your body.

This reaction may involve fever, which is cardinal and always here, but also variation in your blood pressure decrease in your blood pressure. Sometimes decrease oxygenation of your lung. Being short of breath and in when it's more severe effect, you have a malaise and the need to be hospitalized, admitted for, hydration and eventually using drugs to fight against that.

So the side effects are common during the first treatment with bispecific during the first injection. So both bispecific and all that are in development always use what we call step up dosing which means that the first dose of the bispecific antibodies is a very small dose. Then the second dose one week later is a higher dose, then the third week a higher dose to avoid major CRS.

So still those happens. And we have both prevention prophylactic measures such as drugs that will prevent this activation. But also if that happens, way to refrain the severity of the bispecifics of the CRS. Overall what we aim to do is to deliver these drugs as outpatient.

However, when we get to the higher dose, we may need to admit patient for 24 hours to be on the safe side, particularly patients that are older or patient with co-morbidity or patient who don't have a caregiver at home or enough support to be in relationship with the hospital.

But what we organize is really a care that will allow the majority of patients to be always linked to the hospital and always communicate with our care team in order to continue to manage patients with a limited grade CRS, what we CRS stress grade one, at home and being monitored actively to prevent those.

So that's the first major side effect. There have been description of neurological side effects, the same one we see with CAR-T cell.

We call that immune cells.

Side effect associated neurological syndromes. These are very rare. Only 2 or 3 persons, rarely very severe. And, you know, it's a little bit unclear how they, obtain the side effect.

There are two other important effects to know, one is that bispecific deplete normal B cells from the body of patients.

Actually these patient unfortunately already have B-cell depletion from previous treatment. But because of that they are more vulnerable to infections. And they will have also no efficacy of any vaccination during the treatment but also several months after the treatment.

So we have, first of all, to consider that if possible, patients should get some vaccination before the treatment because that will involve flu, pneumonia, Covid, shingles and other disease.

So being vaccinated before receiving this treatment is important as a safety because it won't work and because of these vulnerability. And we will also recommend usually some prophylactic antiviral drugs, antibiotics eventually for patients to prevent these infections and monitor them closely.

Sometimes there is also a decrease in white blood cell, but that's temporary and very different from the one we observe with chemotherapy.

Overall, most patients receive this treatment in the ambulatory setting, and we do manage the side effect quite nicely or quite wisely I will say. They occur mostly, the CRS, during the first cycle. So during the first three four weeks they are very rare. Afterwards. And I will say the experience that patients report to us is that this is an easier treatment than most chemotherapies they have already received.