Table 2. Rates of undetectable minimal... | American Society of Hematology

Table 2.

Rates of undetectable minimal residual disease in bone marrow at the end of targeted combination therapy in TN CLL

Reference	Phase	Treatment	Duration of therapy	Time point of MRD assessment	N	Patient population	MRD method	BM-uMRD, %
CLL14¹⁶	3	VO	12C	EoT	216	Comorbidities +, 12% TP53 aberration, 61% U-IGHV	ASO-PCR	57
CLL13¹²	3	VR VO IVO	12C^a	EoT EoT EoCT	237 229 231	Fit, excluded TP53 aberration, 56% U-IGHV	FC	43 73 78
GLOW³⁵	3	IV	15C	EoCT	106	Age ≥65 years or comorbidities +, excluded TP53 aberration, 58% U-IGHV	NGS	52
CAPTIVATE^36,37	2	IV	15C (fixed duration cohort) 15C (MRD cohort)	EoCT Best MRD	159	Age ≤70 years, 17% TP53 aberration, 56% U-IGHV	FC	62 68^e
MDACC⁴⁵	2	IV	27C^b	EoCT	80	23% TP53 aberration, 83% U-IGHV	FC	66
OSU³⁸	2	IVO	14C	EoCT	25	12% deletion 17p, 71% U-IGHV	FC	67
CLL2-GIVe³⁹	2	IVO	15C or 36C^c	EoCT	41	All with TP53 aberration, 78% U-IGHV	FC	66
DFCI⁴⁰	2	AVO	15C or 24C^d	EoCT	37	27% TP53 aberration, 73% U-IGHV	FC	86
BOVEN⁴¹	2	ZVO	7C+ (MRD guided)	Best MRD	47	13% TP53 aberration, 72% U-IGHV	FC	89

Reference	Phase	Treatment	Duration of therapy	Time point of MRD assessment	N	Patient population	MRD method	BM-uMRD, %
CLL14¹⁶	3	VO	12C	EoT	216	Comorbidities +, 12% TP53 aberration, 61% U-IGHV	ASO-PCR	57
CLL13¹²	3	VR VO IVO	12C^a	EoT EoT EoCT	237 229 231	Fit, excluded TP53 aberration, 56% U-IGHV	FC	43 73 78
GLOW³⁵	3	IV	15C	EoCT	106	Age ≥65 years or comorbidities +, excluded TP53 aberration, 58% U-IGHV	NGS	52
CAPTIVATE^36,37	2	IV	15C (fixed duration cohort) 15C (MRD cohort)	EoCT Best MRD	159	Age ≤70 years, 17% TP53 aberration, 56% U-IGHV	FC	62 68^e
MDACC⁴⁵	2	IV	27C^b	EoCT	80	23% TP53 aberration, 83% U-IGHV	FC	66
OSU³⁸	2	IVO	14C	EoCT	25	12% deletion 17p, 71% U-IGHV	FC	67
CLL2-GIVe³⁹	2	IVO	15C or 36C^c	EoCT	41	All with TP53 aberration, 78% U-IGHV	FC	66
DFCI⁴⁰	2	AVO	15C or 24C^d	EoCT	37	27% TP53 aberration, 73% U-IGHV	FC	86
BOVEN⁴¹	2	ZVO	7C+ (MRD guided)	Best MRD	47	13% TP53 aberration, 72% U-IGHV	FC	89

A, acalabrutinib; ASO-PCR, allele-specific oligonucleotide polymerase chain reaction assay; C, cycles; CIRS, cumulative illness rating scale; CrCl, creatinine clearance; EoCT, end of combination therapy with targeted agents; EoT, end of therapy; FC, flow cytometry; I, ibrutinib; MRD, minimal residual disease; NGS, next-generation sequencing; O, obinutuzumab; R, rituximab; V, venetoclax; Z, zanubrutinib.

In the IVO arm, patients with detectable MRD were allow to continue ibrutinib for up to 36 cycles.

Patients with MRD detectable disease after 27 cycles continued ibrutinib thereafter.

Patients who achieved undetectable MRD at 9 and 12 cycles stopped therapy after cycle 15. All others received 36 cycles.

Treatment cessation was optional for patients who achieved MRD undetectable CR at cycle 15 or 24.

At prerandomization phase, 68% of all-treated patients (72% of evaluable patients) achieved undetectable MRD in bone marrow. At randomization, the study applied stringent criteria for confirmed undectable MRD, which was undetectable MRD serially over at least 2 assessments 3 months apart or longer, and in both blood and bone marrow, at the end of combination therapy. 58% of patients had confirmed undetectable MRD and were randomized 1:1 to placebo or ibrutinib monotherapy. Those with unconfirmed undetectable MRD were randomized 1:1 to ibrutinib or ibrutinib plus venetoclax.

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