Tandem Meetings 2026 | Post-infusion ALCpeak predicts delayed neurotoxicity in patients with myeloma receiving cilta-cel

So previously, there has been clinical trial data, a post-hoc analysis from the CARTITUDE-1 cohort where retrospectively it was looked and found that there were a few risk factors for these delayed neurotoxicities, particularly Parkinsonism. And what they found was high disease burden was one of them, patients with a more inflammatory profile, and patients who actually had higher day seven, day 14, day 21 lymphocyte counts. Subsequently, in a real-world cohort, my investigators at the Mayo Clinic then plotted serial Absolute Lymphocyte Count (ALC) in all the patients receiving cilta-cel. And what we found using ROC analysis was that an ALC peak of greater than 3 times 10 to the power of 9 per liter was quite predictive in determining who developed these delayed neurotoxic disease versus those who did not. And subsequently, based on our study, we found that patients who had an ALC peak, which usually occurs in the second week after cilta-cel infusion, so around day 10 to day 14, about 25 to 30% of patients actually went on to develop the delayed neurotoxic disease, whether they are cranial nerve palsies or Parkinsonism. And that threshold value has subsequently been investigated by other investigators from other hospitals. But what we also strikingly found was that with this threshold, it had a very high negative predictive value, meaning that if your ALC did not go above 3, it seems that you had a close to 0% chance or 99% negative predictive value of developing these toxicities. We didn’t find any difference in efficacy between high ALC versus low ALC, which was interesting, suggesting that there is this ALC sweet spot that I guess we would like to achieve. 

So subsequently, based on these findings, we were thinking to ourselves, will we use risk mitigation strategies to basically modulate this ALC peak, dampen this ALC peak? And we thought about, all right, we’ll use dexamethasone. It’s easy to administer. You can give it in oral form. And we know that the use of dexamethasone did not significantly impair CAR-T efficacy, I guess, extrapolated from the lymphoma CARs. So what we did was, and that was also based on a study by Turner et al., which was presented at Tandem 2025, where they found that potentially using a regimen of 10 milligrams twice daily (BID) of dexamethasone for three days seems to maybe mitigate the risk of these delayed neurotoxicities. So starting from December 2024, the Mayo Clinic basically instituted this dexamethasone prophylaxis regimen, 10 milligrams BID for three days once ALC exceeded three or when it rapidly approaches three, meaning a doubling of the ALC and exceeding 2.5 we start using this 10 milligrams BID of dexamethasone. And we treated maybe about 50 to 60 patients with high ALC peak. And obviously, this brings us to our presentation at Tandem this year with regards to the outcomes of this cohort treated with prophylactic dexamethasone compared to the historical cohort that I previously published in Blood Cancer Journal.

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