****** forwarded me your email about your concerns about Azer Cel toxicity. What people are referring to is a talk given at a CAR-T conference a few months ago. Here's a link to the conference:
Look for Bijal Shah's presentation: "Updates for allo CAR-T PBCAR0191".
Bijal Shah is basically presenting a developmental history of Azer Cel. He talks about the different trials they ran using various lymphodepletion (chemotherapy) and dosing combinations. In the video presentation he walks you through the various trials and discusses the results.
In summary, they found out that certain combinations produced powerful results (100% CRs)...but with serious grade 5 side effects (including death). Their goal was to produce a "good" CAR-T drug with minimal side effect. So they chose the combination that had virtually no side effects with "good" levels of efficacy. Not the "best" efficacy.
IMU is selecting patients that have failed of autologous CAR-T drugs.The trial data showed that this patient cohort had even better results. This group should provide an additional "bump" in the efficacy numbers with excellent overall safety.
All CAR-T drugs require lymphodepletion. This basically wipes out the patient's immune system. This can leave a patient vulnerable to infections, much like with AIDs. This step is necessary to give the CAR-T cells the best chance at survival. So the key is to come up with the best "cocktail". Balancing CAR-T killing power with patient safety.
So yes, Leslie and company certainly knew the developmental history of Azer Cel. They certainly knew the parameter boundaries that shape patient outcomes--in terms of efficacy and safety. The balance.
My understanding is that the current Azer Cel expansión study is using the "sweet spot", in terms of dosing and lymphodepletion. So there should be no worries about toxicity.
The professor
