Table 1.

A comparison of CD123-targeting therapies

Class	Conjugated antibodies	Bispecific antibodies	CAR T cells
Availability for administration	Immediate, off-the-shelf product and not patient specific	Immediate, off-the-shelf product and not patient specific	Requiring manufacturing, however, off-the-shelf allogeneic CARs are in development
Method of administration	IV at repeated doses	Varies from continuous IV infusion to long half-life BiTEs given as repeated IV dosing	Usually single IV infusion
Lymphodepletion	Not required	Not required	This is usually required
FDA approval	Only tagraxofusp is approved for BPDCN	None yet	None yet
Stages in clinical studies	Varied from phase 1 studies to phase 1b/II studies (IMGN632)	Varied from phase 1 (JNJ-63709178, APVO436, XmAb14045) to phase 2/registry studies (flotetuzumab)	Early phases
In combination therapy	Actively being tested (tagraxofusp or IMNG632 in combination venetoclax + HMA)	Actively being tested (flotetuzumab + MGA012)	No, but dual “multi-target” CAR T cells are being tested
Main toxicity	VOD, CLS	CRS	CRS
Product half-life	Intermediate to long	Usually very short, although, there are long half BiTEs (XmAb14045)	Usually long but depends on the co-stimulatory domain and other characteristics

BiTE, bispecific T cell engager; BPDCN, blastic plasmacytoid dendritic cell neoplasm; CAR, chimeric antigen receptor; CLS, capillary leak syndrome; CRS, cytokine release syndrome; HMA, hypomethylating agent; IV, intravenous; VOD, veno-occlusive disease.