Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network

Hermine, Olivier; Hoster, Eva; Walewski, Jan; Bosly, André; Stilgenbauer, Stephan; Thiéblemont, Catherine; Szymczyk, Michał; Bouabdallah, Réda; Kneba, Michael; Hallek, Michael; Salles, Gilles; Feugier, Pierre; Ribrag, Vincent; Birkmann, Josef; Forstpointner, Roswitha; Haı̈oun, Corinne; Hänel, Mathias; Casasnovas, Olivier; Finke, Jürgen; Peter, Norma; Bouabdallah, Kamal; Sebban, Catherine; Fischer, Thomas; Dührsen, Ulrich; Metzner, Bernd; Maschmeyer, Georg; Kanz, Lothar; Schmidt, Christian; Delarue, Richard; Brousse, Nicole; Klapper, Wolfram; Macintyre, Elizabeth; Delfau‐Larue, Marie‐Hélène; Pott, Christiane; Hiddemann, Wolfgang; Unterhalt, Michael; Dreyling, Martin

doi:10.1016/s0140-6736(16)00739-x

Cited by 349 publications

(330 citation statements)

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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.…”

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confidence: 90%

“…For example, the superior outcome of the cytarabine-containing experimental arm of the "MCL Younger" phase III trial of the European MCL Network was heralded by a higher rate of MRD clearance many years before publication of the final results. 5,15 MRD can provide an early prediction of disease recurrence. 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.…”

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confidence: 99%

“…In addition, hypermutated IGH genes may hamper an optimal primer design. Finally, although the predictive role of MRD has been established in MCL, [3][4][5] evidence for the usefulness of subsequent treatment tailoring based on the MRD results is unfortunately still scarce due to the lack of MRD-driven phase III trials in MCL. 8,17 Moreover, no MRD data are available yet in the context of the new targeted treatments, such as the Bruton's tyrosine kinase inhibitor ibrutinib.…”

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confidence: 99%

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Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?

Ferrero

Dreyling

2017

Haematologica

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confidence: 90%

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confidence: 99%

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confidence: 99%

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Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?

Ferrero

Dreyling

2017

Haematologica

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“…Administered appropriately, combinations including high-dose cytarabine and autologous stem cell transplantation can result in remissions nearly a decade long in some younger patients. 6 Less-intensive regimens have also been reported to produce durable remissions, with emerging evidence that patient-related factors and disease biology trump choice of therapy in impacting outcomes. 1,7,8 Moreover, chemotherapy may have some desirable effects beyond simple cytotoxicity: cyclophosphamide may inhibit regulatory T cells (Tregs), 9 doxorubicin may impair myeloidderived suppressor cells, 10 and low-dose metronomic therapy may impact tumor angiogenesis.…”

Section: Why Is There a Need For Nonchemotherapy Options?mentioning

confidence: 99%

The potential for chemotherapy-free strategies in mantle cell lymphoma

Martin

Ruan

Leonard

2017

Blood

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Mantle cell lymphoma (MCL) may be 1 of the few cancers for which multiple chemotherapy and nonchemotherapy regimens are considered as standard. Despite the significant activity of chemotherapy in the first-line setting and beyond, its limitations are reflected in the relatively poor ultimate outcomes of patients with MCL treated in the real world. Patients with highly proliferative MCL and those with TP53 mutations tend to respond poorly despite intensive cytotoxic therapies. Patients with comorbidities and those who are geographically isolated may not have access to the regimens that may appear most promising in clinical trials. Thoughtfully directed, nonchemotherapy agents might overcome some of the factors associated with a poor prognosis, such at TP53 mutation, and might resolve some of the challenges related to the toxicity and deliverability of standard chemotherapy regimens. Several clinical trials have already demonstrated that combinations of nonchemotherapy plus chemotherapy drugs can impact outcomes, whereas data with nonchemotherapy agents alone or in combination have suggested that some patients might be well suited to treatment without chemotherapy at all. However, challenges including chronic or unexpected toxicities, the rational vs practical development of combinations, and the financial acceptability of new strategies abound. The nonchemotherapy era is here: how it unfolds will depend on how we meet these challenges.

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“…This approach produced long-term PFS and a significantly higher proportion of MR and PCR-negative stem cell products as compared with the MCL-1 trial (high dose CHOP followed by ASCT) (37). (63)(64)(65). In particular, prospective quantitative MRD monitoring was a secondary endpoint of the two EuMCLNet phase III trials, namely the "Younger" and the "Elderly".…”

Section: Mantle Cell Lymphomamentioning

confidence: 99%

Personalized Medicine in Lymphoma: Tailoring Treatment According to Minimal Residual Disease

Dogliotti

Ferrero

2017

MRAJ

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Mature B-cell disorders have recently become highly curable diseases thanks to the introduction of new treatment strategies; nonetheless, despite evidence of complete remission, many patients affected by lymphoma or myeloma eventually relapse and need salvage therapy. Minimal residual disease (MRD) detection and quantification is a powerful tool to evaluate treatment efficacy, to stratify patients, and to predict long-term outcome. In fact, in the current landscape of novel, highly efficacious but toxic and often costly targeted therapies, early identification of factors predictive of treatment response or refractoriness is the key to avoid overtreatment of patients and thus also to reduce costs for health care system.In this article, we reviewed the prognostic role of MRD in follicular lymphoma, mantle cell lymphoma and multiple myeloma. We analyzed published clinical studies and available methodologies, and we described the major ongoing studies of MRD-driven tailored treatment in these diseases. Finally, we discussed novel applications and techniques for MRD identification in hematologic malignancies and future directions of MRD-oriented research. In particular, we hypothesized some possible, next-generation, precision medicine trials in lymphoproliferative diseases based on the most promising currently available biomarkers.

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Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network

Cited by 349 publications

References 30 publications

Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?

Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?

The potential for chemotherapy-free strategies in mantle cell lymphoma

Personalized Medicine in Lymphoma: Tailoring Treatment According to Minimal Residual Disease

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