Results of ALLO-715, an allogeneic BCMA-targeting CAR T cell therapy are published.
Novel features to this product:
‼️ Has rituximab kill switch
‼️ Knockout of the T cell receptor alpha constant (TRAC) to reduce GVHD risk
‼️ Knockout CD52
/1 #mmsm
www.nature.com/articles/s41591-022-02182-7

Knocking out cd52 allowed for use of a separate alemtuzumab-like agent ALLO-647 to eradicate cd52 expressing cells (ie all the other T cells) to achieve lymphodepletion without affecting the product.

This is also an allogeneic product, derived from 3 healthy pts. /2

- 3+3 design with 4 doses tested. Multiple LD regimens also tested.
- 5 patients did not proceed due to prog, death, acute events
- 43 proceeded with LD chemo and study therapy
👍median time from enrollment to LD chemo 5 days!
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42% had penta-refractory disease. 3 pts had prior bcma directed therapy.

1 DLT: fungal PNA (death)

CRS rate 56%. Neurotox 14%. Infections 54% (23% G3). Cmv Viremia 33%. 3 deaths due to infection.

ORR 56%. ORR 71% at higher doses. mDOR 8.3 months.
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Lots of cool science and a very worthy read. Kudos to the team.

Too early to tell, but my concerns:
- High rates of CMV viremia. Overcome potentially with ppx?
- Duration of response leaves much to be desired. Problem with persistence? (67% w/out detectable CAR T by 28 days).