Table 4 Representative treatments shown to induce MRD in CLL.

From: Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations

Study

Line

Agent

Type

N

Assay

U-MRD

Goede et al. [44]

First

G + clb vs

R + clb

Ph 3

474

ASO-PCR

GClb:19.5% (BM), 37.7% (PB)

RClb: 2.6% (BM), 3.3% (PB)

Hillmen et al. [51]

First

Ofa + clb vs Clb

Ph 3

212

NS

Ofa + clb: 8% (BM or PB)

Eichhorst et al. [48]

First

BR vs

FCR

Ph 3

561

Flow MRD4

BR: 11% (BM)

FCR: 27% (BM)

Sharman et al. [52]

First

BG

Ph 2

102

Flow MRD4

Best response: 75.5% (PB)

Stilgenbauer et al. [53]

First

BG

Ph 3b

158

Flow MRD4

27.8% (BM), 59.5% (PB)

Leblond et al. [54]

First

GFC

Ph 3

140

Flow MRD4

35.7% (BM), 64.3% (PB)

Böttcher et al. [19]

First

FCR vs

CF

Ph 3

493

Flow MRD4

FCR: 63% (PB)

CF: 35% (PB)

Eichhorst et al. [48]

First

BR vs

FCR

Ph 3

564

Flow MRD4

BR: 11% (BM), 38% (PB)

FCR: 27% (BM), 49% (PB)

Dartigeas et al. [80]

First

FCR ± R maintenance

Ph 3

542

Flow MRD5

36.7% (BM), 59.3% (PB)

Munir et al. [50]

First

FCR vs

FCRM

Ph 2b

215

Flow MRD4

FCR: 50.5% (BM)

FCRM: 43.5% (BM)

Wierda et al. [9]

First

Ibr + ven

Ph 2

163

Flow MRD4

82% (PB)

Rogers et al. [56]

First

G + ibr + ven

Ph 2

25

Flow MRD4

60% (BM), 72% (PB)

Fischer et al. [71]

First

G + ven vs

G + clb

Ph 3

432

ASO-PCR

G + ven: 75.5% (PB), 56.9% (BM)

G + clb: 35.2% (PB), 17.1% (BM)

Stilgenbauer et al. [58]

Any

Ven + BR or BG

Ph 1b

17 (BR)

8 (BG)

Flow MRD4

Ven + BR: 67% (NS)

Ven + BG: 50% (NS)

Cramer et al. [59]

Any

B, then ven + G

Ph 2

63

Flow MRD4

1 L: 12% (BM), 91% (PB)

R/R: 14% (BM), 83% (PB)

Burger et al. [63]

Any

Ibr vs

Ibr + R

Ph 2

208

Flow MRD4

Ibr: 12 mo, 34.4% (BM),

24 mo, 19.8% (BM);

Ibr + R: 12 mo, 18.5% (BM)

24 mo, 12.2% (BM)

Stilgenbauer et al. [42]

Any

Ven

Ph 2

158

Flow MRD

12.7% (BM), 30% (PB)

Rawstron et al. [8]

R/R

Ibr + G

Ph 1

40

MRD4

Ibr-naïve: 30% (PB)

Prior ibr: 60% (PB)

Roberts et al. [64]

R/R

Ven

Ph 1

116

MRD4

5% (BM)

Fraser et al. [7]

R/R

Ibr + BR vs

PBO + BR

Ph 3

578

Flow MRD4

Ibr + BR: 26.3% (PB or BM)

PBO + BR: 6.2% (PB or BM)

P < .0001

Seymour et al. [41]

R/R

Ven + R

vs BR

Ph 3

389

Flow MRD4

ASO-PCR

VenR: 27.3% (BM), 83.5% (PB)

BR: 1.5% (BM), 23.1% (PB)

  1. 1L first-line, ASO-PCR allele-specific oligonucleotide polymerase chain reaction, BG bendamustine and obinutuzumab, BM bone marrow, BR bendamustine and rituximab, CF fludarabine and cyclophosphamide, Clb chlorambucil, Flow flow cytometry, FCR fludarabine, cyclophosphamide, and rituximab, FCRM FCR and mitoxantrone, G obinutuzumab, GFC obinutuzumab, fludarabine, and cyclophosphamide, Ibr ibrutinib, MRD measurable residual disease, PB peripheral blood, Ofa ofatumumab, PBO placebo, Ph phase, R rituximab, Ven venetoclax.
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