I just dug through a recent phase 2 dataset on a CD19xCD3 in moderate SLE, and the week 12 responses looked meaningfully higher than historical controls without the neutropenia spike we saw in 2022. Is this smarter dosing and biomarker gating (baseline BAFF-high, low interferon signature) or a genuine modality step-change — anyone else seeing similar signals or think this is mostly patient selection?
At our site, the cleaner week‑12 readout came after step‑up dosing with steroid premed and gating to “BAFF‑high/low IFN” — felt like swapping a sledgehammer for a scalpel. Durability wobbled by ~week 20 with a small bump in grade 2 infections, so I’d chalk it up to dosing + enrichment rather than a modality step‑change. Practical tip: time the second step to the CD19+ B‑cell nadir (we use day about 10 flow), which saved us a couple of rescues.
We saw a similar week‑12 lift when we capped first‑cycle exposure (AUC target) and used on‑demand toci for IL‑6 spikes, plus gating on “plasmablast‑high/low IFN” rather than BAFF alone, @susan_reeves78. Small caveat: durability sagged post‑steroid taper in anti‑dsDNA‑high patients unless we kept IgG >[redacted]/dL with intermittent IVIG, so I’d call it smarter ops more than a modality leap for now. Kind of like nudging the thermostat instead of swapping the whole HVAC.
One practical tip: we excluded baseline IgG <[redacted]/dL or gave “IVIG day -7,” then split the first CD19xCD3 dose 20/80 over 48 hours; our 3‑month readouts improved and we didn’t see the 2022‑style neutrophil dip. Small caveat: IVIG can muddy BAFF assays and isn’t cheap, so we reserve it for borderline IgG.