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Table 2 Summary of MCL studies using MRD

From: Advances in the assessment of minimal residual disease in mantle cell lymphoma

Author

MRD method/Target

Population

Treatment type

MRD results

Cowan et al. [4]

qPCR and MFC/IgH rearrangement or t(11;14) translocation

Previous ASCT MCL pts in clinical CR

ASCT

MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR

Liu et al. [6]

qPCR/IgH rearrangement

Treatment-naïve MCL pts

R-CHOP

+ASCT*

MRD negativity: 46% (74%*)

Tam et al. [20]

MFC and ASO-qPCR/IgH rearrangement or t(11;14) translocation

R/R MCL pts

Ibrutinib and venetoclax

MRD negativity:

-MFC 67%

-ASO-qPCR 38%

Klener et al. [21]

qPCR/IgH rearrangement

Transplant-ineligible MCL pts who received R-CHOP/R-cytarabine

R-CHOP/R-cytarabine + rituximab maintenance

MRD (positive vs negative) after 3 or 6 cycles of induction therapy not correlated with PFS

Hermine et al. [22]

ASO-qPCR/not specified

Treatment-naïve MCL pts

R-CHOP + ASCT* (control) vs R-CHOP/R-DHAP + ASCT* (cytarabine)

MRD negativity:

-PB: 47% in control and 79% in cytarabine (68%* vs 85%*)

-BM: 26% in control and 61% in cytarbine (59%* vs 68%*)

Kolstad et al. [23]

Nested PCR/IgH rearrangement

Treatment-naïve MCL pts

R-HDS

+ASCT*

MRD negativity: 56% (86%*)

Albertsson-Lindblad et al. [24]

Nested PCR/IgH rearrangement

Treatment-naïve MCL pts

Lenalidomide  + bendamustine + rituximab

MRD negativity:

-After 6 cycles 36%

-Therapy completion: 64%

Kolstad et al. [25]

Combined nested and qPCR/IgH rearrangement

ASCT and PCR marker available MCL pts

ASCT

Possible rituximab maintenance

58 pts experienced MRD relapse and got rituximab maintenance. This converted pts to MRD-(87%) but many became positive again later (69%)

Starza et al. [26]

Nested and qPCR/IgH rearrangements

From 4 labs of the FIL MRD Network: Both MCL and FL pts

N/A

156/187 samples concordantly classified as MRD positive or negative by both methods; 31 samples were borderline

Szostakowska et al. [27]

qPCR/t(11;14), IgH rearrangement, SOX11

MCL pts at diagnosis and treatment

Various

At diagnosis: high SOX11 had shorter PFS vs low SOX11 (p = 0.04)

Drandi et al. [28]

qPCR, MFC, ddPCR/IgH rearrangement

MCL MRD samples from 4 prospective trials of the European MCL Network

N/A

All 3 methods gave comparable results in MRD samples with 0.01% positivity. ddPCR was preferable to qPCR on BQR samples.

Armand et al. [29]

ClonoSeq/IgH rearrangement

Treatment-naïve MCL pts

Rituximab + bendamustine / Rituximab + cytarabine

MRD negativity: 93%

Ruan et al. [30]

ClonoSeq/IgH rearrangement

Treatment-naïve MCL pts

Lenalidomide + rituximab

MRD negativity: 8 out of 10 subjects

Ladetto et al. [31]

qPCR and NGS/IgH rearrangement

ALL, MCL, and MM pts

N/A

NGS had same level of sensitivity as ASO-qPCR

Smith et al. [32]

ClonoSeq and MFC/IgH rearrangement

Treatment-naïve MCL pts

Bendamustine-rituximab + rituximab ± lenalidomide

MRD negativity:

-NGS: 91% PB and 90% BM

-MFC:95% PB

Callanan et al. [33]

qPCR/IgH rearrangement

MCL pts < 66 years of age

R-DHAP

+ASCT* + rituximab maintenance

MRD negativity:

-80% âž” 95%* PB

-66% âž” 82%* BM

  1. qPCR real-time quantitative PCR, MFC multiparameter flow cytometry, IgG immunoglobulin heavy chain, ASCT autologous stem cell transplant, pts patients, CR complete response, R-CHOP rituximab/cyclophosphamide/doxorubicin hydrochloride/vincristine sulfate/prednisone, R/R relapsed/refractory, PFS progression-free survival, PB peripheral blood, BM bone marrow, R-HDS rituximab/high-dose sequential chemotherapy, FL follicular lymphoma, ddPCR digital droplet PCR, BQR below the quantitative range samples, ALL acute lymphocytic leukemia, MM multiple myeloma, NGS next-generation sequencing, R-DHAP rituximab/dexamethasone/cytarabine/cisplatin