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The metronomic all-oral DEVEC is an effective schedule in elderly patients with diffuse large b-cell lymphoma

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Summary

Metronomic-chemotherapy (M-CHT) has been rarely assessed in non-Hodgkin-lymphoma (NHL). Therefore, in 2011 we started experimenting a new all-oral M-CHT schedule termed DEVEC (Deltacortene®, etoposide, vinorelbine, cyclophosphamide, +/-Rituximab) in diffuse-large-B-cell lymphoma (DLBCL) patients. Methods Patients with stage Ib-IV were enrolled as follows: 1) treatment-naïve, frail ≥65y, or unfit ≥85y; and 2) relapsed/refractory (R/R) ≥55y. Data were prospectively collected from six Italian centres and compared for efficacy to two reference groups, treated with established iv Rituximab-CHT in 1st and 2nd line respectively. Results from April-2011 to March-2018, 17/51(33%) naïve, 21/51(41%) refractory and 13/51(25.5%) relapsed patients started DEVEC; 39/51(76.5%) were de-novo DLBCL; 10/51(19.6%) transformed-DLBCL and 2/51(3.9%) unclassifiable-DLBCL/classical-Hodgkin-lymphoma. The median age was 85y (range=77-93) and 78y (range=57-91) in naïve and R/R respectively and overall the DEVEC patients had very poor features compared to the reference. The rate of grade≥3 haematological-AEs was 43%(95CI=29-58%): G3-neutropenia was the most frequent; grade≥3 extra-haematological-AEs was 13.7% (95%CI=5.4-25.9%), the most frequent was infection. One-year OS and PFS were 67% and 61% for naive, 60% and 50% for reference-naïve respectively; Cox proportional hazard ratio (Cox-PH-ratio) for OS and PFS were 0.69 (95%CI=0.27-1.76;p=.441) and 0.68 (95%CI=0.28-1.62;p=.381) respectively. One-year OS and PFS were 48% and 39% in the R/R, 36% and 17% in the reference-R/R respectively; Cox-PH-ratio for OS and PFS, were 0.76 (95%CI=0.42-1.40; p=.386) and 0.48 (95%CI=0.28-0.82; p=.007) respectively. Conclusion The favourable activity of DEVEC compared to a real-life series and the convenience of an oral administration, may possibly lay the groundwork for a paradigm-shift in the treatment of elderly DLBCL.

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Acknowledgments

M Christina Cox : performed the research, designed the research study, analysed the data, wrote the paper.

Sabrina Pelliccia: performed the research, analysed the data, wrote the paper

Luigi Marcheselli: designed the research study, analysed the data, wrote the paper

Roberta Battistini: performed the research, wrote the paper

Annalisa Arcari: performed the research, designed the research study, wrote the paper

Paola Anticoli Borza: performed the research, wrote the paper

Caterina Patti: performed the research, wrote the paper

Ivana Casaroli: performed the research, wrote the paper

Francesca di Landro: performed the research, wrote the paper

Arianna Di Napoli: performed the research, wrote the paper wrote the paper

Francesca Fabbri: performed the research, wrote the paper

Matteo Caridi: analysed the data, wrote the paper

Agostino Tafuri: performed the research, wrote the paper

Guido Bocci: designed the research study, analysed the data, wrote the paper

Gerardo Musuraca: performed the research, designed the research study, analysed the data, wrote the paper

Funding

The work was supported by the Department of Oncological science, Azienda Ospedaliera-Universitaria Sant’Andrea, Rome, Italy

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Authors and Affiliations

  1. Haematology Department, King’s College Hospital NHS Foundation Trust, London, UK

    M. Christina Cox

  2. Hematology Unit, Azienda Ospedaliera Universitaria Sant’Andrea, Rome, Italy

    M. Christina Cox, Sabrina Pelliccia & Agostino Tafuri

  3. Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell’Adulto, Università degli studi di Modena e Reggio Emilia, Modena, Italy

    Luigi Marcheselli

  4. Hematology Unit, AO San Camillo Forlanini, Rome, Italy

    Roberta Battistini

  5. Hematology Unit, Ospedale Guglielmo da Saliceto di Piacenza, Piacenza, Italy

    Annalisa Arcari

  6. Hematology Unit, A.O. San Giovanni Addolorata, Rome, Italy

    Paola Anticoli Borza

  7. Hematology Unit, ’0spedale V. Cervello, Palermo, Italy

    Caterina Patti

  8. Hematology Unit, Ospedale San Gerardo, Monza, Italy

    Ivana Casaroli

  9. Hematology Unit, Policlinico Universitario Agostino Gemelli, Rome, Italy

    Francesca di Landro

  10. Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy

    Arianna Di Napoli, Matteo Caridi & Agostino Tafuri

  11. Hematology Unit, IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy

    Francesca Fabbri & Gerardo Musuraca

  12. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Guido Bocci

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Correspondence to M. Christina Cox or Guido Bocci.

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Conflict of Interest

Author M Christina Cox declares that she has no conflict of interest;

Author Sabrina Pelliccia, declares that she has no conflict of interest,

Author Luigi Marcheselli, declares that he has no conflict of interest;

Author Roberta Battistini, declares that she has no conflict of interest;

Author Annalisa Arcari, declares that she has no conflict of interest;

Author Paola Anticoli Borza, declares that she has no conflict of interest;

Author Caterina Patti , declares that she has no conflict of interest;

Author Ivana Casaroli , declares that she has no conflict of interest;

Author Francesca di Landro , declares that she has no conflict of interest;

Author Arianna Di Napoli, declares that she has no conflict of interest;

Author Francesca Fabbri, declares that she has no conflict of interest;

Author Matteo Caridi, declares that he has no conflict of interest;

Author Agostino Tafuri , declares that he has no conflict of interest;

Author Guido Bocci , declares that he has no conflict of interest;

Author Gerardo Musuraca,, declares that he has no conflict of interest;

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Sapienza ethics committee (EC approval n° 4640).

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Cox, M.C., Pelliccia, S., Marcheselli, L. et al. The metronomic all-oral DEVEC is an effective schedule in elderly patients with diffuse large b-cell lymphoma. Invest New Drugs 37, 548–558 (2019). https://doi.org/10.1007/s10637-019-00769-5

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