Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study

Pott, Christiane; Hoster, Eva; Delfau‐Larue, Marie‐Hélène; Beldjord, Kheïra; Böttcher, Sebastian; Asnafi, Vahid; Plonquet, Anne; Siebert, Reiner; Callet‐Bauchu, Evelyne; Andersen, Niels Smedegaard; Dongen, Jacques J. M. van; Klapper, Wolfram; Berger, Françoise; Ribrag, Vincent; Hoof, Achiel L. van; Trněný, Marek; Walewski, Jan; Dreger, Peter; Unterhalt, Michael; Hiddemann, Wolfgang; Kneba, Michael; Kluin-Nelemans, Hanneke C.; Hermine, Olivier; Macintyre, Elizabeth; Dreyling, Martin

doi:10.1182/blood-2009-06-230250

Cited by 244 publications

(239 citation statements)

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“…At initial diagnosis, the infiltration level in PB and BM was shown to be comparable in the MCL Younger and MCL Elderly trials, 17 but it has been consistently observed that during and after treatment, PB is more frequently and more rapidly cleared of MRD than BM. In the MCL Younger and MCL Elderly trials, we observed that analysis of PB alone failed to demonstrate persistent lymphoma cells at the end of induction in about 15% of patients who were simultaneously positive in BM.…”

Section: Source Of Materials For Mrd Assessmentmentioning

confidence: 98%

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Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Hoster

Pott

2016

Hematology

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Despite the recent substantial improvement of clinical outcome in mantle cell lymphoma (MCL), resistance to immunochemotherapy and common relapses are challenges for long-term tumor control. The assessment of minimal residual disease (MRD) by real-time quantitative polymerase chain reaction has emerged as a widely feasible and standardized tool for direct assessment of therapy-induced reduction of tumor burden and regrowth after cytotoxic treatment in MCL, with much improved sensitivity compared with conventional staging procedures. Several studies have shown that intensification of initial treatment, which has resulted in improved clinical outcome, is immediately reflected in higher molecular remission rates; they have also shown that high-dose consolidation might not be able to compensate for less intensive induction regimens. Persistence or reappearance of MRD in clinical remission proved to be highly predictive for imminent clinical relapse associated with shorter overall survival. Therefore, the investigation of novel MRD-guided treatment strategies aimed at early eradication of MRD and pre-emptive treatment of molecular relapse seems warranted. Furthermore, the integration of MRD assessment into clinical response criteria could result in a more specific and potentially earlier end point for treatment efficacy. New technical developments such as high-throughput sequencing will further enhance the wide applicability of MRD detection in MCL.Learning Objectives

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Section: Source Of Materials For Mrd Assessmentmentioning

confidence: 98%

“…diagnosis of 6.3 3 10 22 . 17 However, RQ-PCR for both targets is restricted to those patients with junctional regions suited to reach sufficient sensitivity by applying the published guidelines. 18 By applying the guidelines, 86% of the MCL Younger and MCL Elderly trial cohorts were reliably quantifiable by RQ-PCR.…”

Section: Rq-pcrmentioning

confidence: 99%

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Hoster

Pott

2016

Hematology

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“…Even in the context of an incurable disease like MCL, the deepness of treatment response measured by MRD widely reflects patient outcome in large, prospective trials. [3][4][5] The predictive role of MRD analysis in MCL was confirmed in different patient subsets (both younger and elderly), treatment strategies (autologous transplantation and conventional immuno-chemotherapy), tissues (bone marrow and peripheral blood) and time points (end of induction and during maintenance treatment). 4 MRD allows for risk stratification of patients after treatment.…”

mentioning

confidence: 89%

“…[3][4][5] The predictive role of MRD analysis in MCL was confirmed in different patient subsets (both younger and elderly), treatment strategies (autologous transplantation and conventional immuno-chemotherapy), tissues (bone marrow and peripheral blood) and time points (end of induction and during maintenance treatment). 4 MRD allows for risk stratification of patients after treatment. MRD describes the efficacy of therapy and presence of even minimal, resistant tumor clones; thus, this approach identifies patients at higher risk of recurrence after an apparently successful treatment.…”

mentioning

confidence: 89%

“…Only selected laboratories across Europe have so far been certified by the Euro MRD consortium, a standardization group regularly performing quality control rounds for MRD analysis in leukemia and lymphoma (http://www.euromrd.org). 18 Only by standardized analyses in this laboratory network can reliable MRD results be obtained in large, international clinical trials, such as the 4 In particular, patients with low or absent bone marrow invasion often do not carry a marker and cannot, therefore, be analyzed for MRD. In addition, hypermutated IGH genes may hamper an optimal primer design.…”

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confidence: 99%

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