IMS 2026 | Prophylactic cyclophosphamide for delayed neurotoxicity after cilta-cel in multiple myeloma

So in clinical practice now, we have the potential opportunity to use CAR-T cell therapy for patients as early as second-line treatment after they become enzalutamide refractory. And it’s very exciting that we’ve seen overall survival advantage too from randomized control studies compared to conventional triplets in addition to the primary endpoint of prolonged progression-free survival. However, despite some of these strategies to try to reduce disease burden going in, there’s still a very small percent of the patients, likely somewhere around 1% of the patients, who may be at risk for developing some delayed neurotoxicities, such as ICANS-associated Parkinsonism. And so even though it’s rare, because these symptoms can last, and previously we were seeing more severe manifestations of that, it’s important for us to see what we can do to reduce the risk for patients to develop this. And so we have recently published our experience where we found that for patients during the time of CAR-T cell expansion, if their lymphocyte count gets above the normal range, so for a clinical lab that is typically around three, when it gets above three, the risk of developing Parkinsonism goes from somewhere around 1% to likely around 12%, so it gets higher. So it is that patient population that we try to do some early preventative strategies. So previously we have done prophylactic dexamethasone or steroid strategy where a patient may get dexamethasone for around three days until the lymphocyte counts start to drop. And we saw in that cohort that it didn’t reduce the incidence of Parkinsonism. And we still had patients with quite severe manifestation, including some patients who have died from the complications of either Parkinsonism or treatment. So at ASH 2026, we present our most recent experience where we changed from using dexamethasone to cyclophosphamide. So we were giving a one-time dose, 500 milligram, similar to the dose that we would normally give for a weekly Cytoxan D, but just one time when the patient’s lymphocyte count gets at or above three, so above the normal threshold. Unfortunately, what we’ve seen with close to 56 patients treated with this strategy is that we’re not seeing a reduction in the incidence of Parkinsonism. However, we are seeing that these patients are presenting with much milder symptoms, and many of them are either improving or have symptoms that are resolved at the time of presentation with relatively milder treatment. So it may be that there’s some qualitative improvement in the severity of the symptoms when they manifest with this approach. But it could also be there’s a factor of more education with the patient and caregivers so they’re coming back to us for evaluation earlier as well so the earlier intervention may be more effective.

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