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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% ➔ 95%* PB
-66% ➔ 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