The Role of BTK Inhibition in the Treatment of Chronic Lymphocytic Leukemia: A Clinical View

Figures & data

Figure 1 B Cell Receptor Signaling Pathway and Inhibition of BTK. Surface membrane of a B cell demonstrating surface B cell receptor and down-stream signaling molecules that participate in providing pro-survival, proliferation, migration, and apoptosis signals to the B cell, including CLL cells. Inhibitors of BTK that block this signaling are shown below, including inducers of degradation, irreversible and reversible inhibitors of BTK kinase activity.

Table 1 Select Currently Active Phase III First-Line Trials with Irreversible BTK-i for CLL

Trial	Population	N	Status	MRD	Treatment ARMS
CLL12	≥18 yo, High Risk of Disease Progression	515	Enrolled	Secondary	Ibr			Observation
NCT02863718			Pending
EA9161	Fit, 18–69 yo	720	Enrolled	Secondary	IbrVenOb	IbrOb
NCT03701282			Pending
GLOW	≥ 65 yo, or unfit pts	211	Enrolled	Secondary	IbrVen			ChlOb
NCT03462719			Reported
GAIA/CLL13	≥18 yo, Fit patients	926	Enrolled	Primary	IbrVenOb	VenOb	VenR	FCR/BR
NCT02950051			Pending
E1912	18–70 yo, Fit patients	519	Enrolled	No	IbrR			FCR
NCT02048813			Reported
ELEVATE-TN	≥18 yo	535	Enrolled	Secondary	AcaOb	Aca		ChlOb
NCT02475681			Reported
A041702	≥70 yo or ≥ 65 yo with del (17p)	454	Enrolling	Secondary	IbrVenOb	IbrOb
NCT03737981
CLL17	≥18 yo	897	Enrolling	Secondary	Ibr	VenOb	IbrVen
NCT04608318
NCT04075292	≥18 yo	150	Enrolling	Secondary	Aca			ChlR
ACE-CL-311	≥18 yo	780	Enrolling	Secondary	AcaVenOb	AcaVen		FCR/BR
NCT03836261
GLLC-EARLY	≥18 yo, High-risk for early progression	130	Enrolling	Secondary	Aca			Observation
NCT04178798
SEQUOIA	All patients	710	Enrolling	Secondary	Zan	ZanVen in CLL with del(17p)		BR
NCT03336333

Abbreviations: Aca, acalabrutinib; BR, bendamustine, rituximab; Chl, chlorambucil; FCR, fludarabine, cyclophosphamide, rituximab; Ibr, ibrutinib; MRD, minimal residual disease; N, number; Ob, obinutuzumab; Ven, venetoclax; yo, years old; Zan, zanubrutinib.