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Lymphoma

Outcomes in first relapsed-refractory younger patients with mantle cell lymphoma: results from the MANTLE-FIRST study

Leukemia volume 35, pages 787–795 (2021)Cite this article

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A Correction to this article was published on 22 January 2021

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Abstract

Patients with mantle cell lymphoma (MCL) that fail induction treatment represent a difficult-to-treat population, where no standard therapy exists. We evaluated outcomes in patients with first relapsed-refractory (r/r) MCL after upfront high dose cytarabine including standard regimens. Overall survival (OS-2) and progression-free survival (PFS-2) were estimated from the time of salvage therapy. The previously described threshold of 24 months was used to define patients as early- or late-progressors (POD). Overall, 261 r/r MCL patients were included. Second-line regimens consisted of rituximab-bendamustine (R-B, 21%), R-B and cytarabine (R-BAC, 29%), ibrutinib (19%), and others (31%). The four groups were balanced in terms of clinicopathological features. Adjusting for age and early/late-POD, patients treated with R-BAC had significantly higher complete remission (63%) than comparators. Overall, Ibrutinib and R-BAC were associated with improved median PFS-2 [24 and 25 months, respectively], compared to R-B (13) or others (7). In patients with early-POD (n = 127), ibrutinib was associated with inferior risk of death than comparators (HR 2.41 for R-B, 2.17 for others, 2.78 for R-BAC). In patients with late-POD (n = 134), no significant differences were observed between ibrutinib and bendamustine-based treatments. Ibrutinib was associated with improved outcome in early-POD patients.

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Fig. 1: Survival curves according to second line therapy.
Fig. 2: Survival curves for patients with early-POD.
Fig. 3: Survival curves for patients with late-POD.
Fig. 4

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Acknowledgements

The authors are grateful to the patients who participated in the study, their family, friends and caregivers, the study staff and health care providers. The authors thank Benedetta Puccini (Firenze), Annalisa Arcari (Piacenza), Irene Dogliotti (Torino University), Dario Marino (Padova), Michele Merli (Varese), Francesco Piazza (Padova), Massimo Gentile (Cosenza), Matteo Pelosini (Pisa), Giacomo Loseto (Bari), and AnnaLia Molinari (Rimini) who provided data. We thank Emilia Elizbeta Florea (Verona) for the precious administrative support to the research. All authors participated in patients’ enrollment, defined tumor response, and provided information in regard to clinical questions and follow-up. Each contributing center abstracted patient-level data by using criteria defined in the MANTLE-FIRST research proposal using a standardized, investigator-developed data entry form.

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Authors and Affiliations

  1. Department of Medicine, Section of Hematology, University of Verona, Verona, Italy

    Carlo Visco, Francesca Maria Quaglia, Cristina Tecchio & Mauro Krampera

  2. Department of Translational and Precision Medicine, Sapienza University, Rome, Italy

    Alice Di Rocco & Luca Petrucci

  3. Unit of Clinical Epidemiology, Azienda Ospedaliera Universitaria Città della Salute e della Scienza and CPO Piemonte, Turin, Italy

    Andrea Evangelista

  4. Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy

    Maria Chiara Tisi

  5. Unit of Hematology, Humanitas Clinical and Research Center, Milan, Italy

    Lucia Morello & Monica Balzarotti

  6. Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Vittorio Ruggero Zilioli & Chiara Rusconi

  7. Hematology and Bone Marrow Transplantation, IRCSS Istituto Nazionale Tumori, Milan, Italy

    Chiara Rusconi & Annalisa Chiappella

  8. Hematology, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy

    Stefan Hohaus

  9. Haematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Roberta Sciarra & Luca Arcaini

  10. Hematology, Spedali Civili, Brescia, Italy

    Alessandro Re

  11. Hematology, “Città della Salute e della Scienza di Torino” University Hospital, Turin, Italy

    Annalisa Chiappella

  12. Hematology, Vall d’Hebron Institut of Oncology, Barcelona, Spain

    Ana Marin-Niebla

  13. Haematology, University of Plymouth and Derriford Hospital, Plymouth, United Kingdom

    Rory McCulloch & Simon Rule

  14. Hematology, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy

    Guido Gini

  15. Hematology, University of Bari, Bari, Italy

    Tommasina Perrone

  16. Hematology, Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy

    Luca Nassi

  17. Hematology, UOSD “Centro Diagnosi e Terapia dei Linfomi”, PO Santo Spirito, Pescara, Italy

    Elsa Pennese

  18. Hematology, General Hospital Ca’ Foncello, Treviso, Italy

    Piero Maria Stefani

  19. Hematology, AOU Sant’Andrea, Rome, Italy

    Maria Christina Cox

  20. Hematology, P.O. V. Fazzi, Lecce, Italy

    Valentina Bozzoli

  21. Hematology, Azienda Ospedaliera Universitaria Senese & University of Siena, Siena, Italy

    Alberto Fabbri

  22. Hematology, Ospedale degli Infermi, Rimini, Italy

    Valentina Polli

  23. Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Torino/”Città della Salute e della Scienza di Torino” University Hospital, Turin, Italy

    Simone Ferrero

  24. Hematology, AUSLL/IRCCS Santa Maria Nuova Hospital, Reggio Emilia, Italy

    Maria Isabel Alvarez De Celis

  25. Hematology, Policlinico di Napoli, Napoli, Italy

    Antonello Sica

  26. Candiolo Cancer Institute, FPO-IRCCS, Candiolo (Turin), Italy

    Umberto Vitolo

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  1. Carlo Visco
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  15. Rory McCulloch
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  16. Guido Gini
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  18. Luca Nassi
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  19. Elsa Pennese
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  20. Piero Maria Stefani
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  21. Maria Christina Cox
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  22. Valentina Bozzoli
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  23. Alberto Fabbri
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  24. Valentina Polli
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  25. Simone Ferrero
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  26. Maria Isabel Alvarez De Celis
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  27. Antonello Sica
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  28. Luca Petrucci
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  29. Luca Arcaini
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Correspondence to Carlo Visco.

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Visco, C., Di Rocco, A., Evangelista, A. et al. Outcomes in first relapsed-refractory younger patients with mantle cell lymphoma: results from the MANTLE-FIRST study. Leukemia 35, 787–795 (2021). https://doi.org/10.1038/s41375-020-01013-3

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