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Dose-dense ABVD as first-line therapy in early-stage unfavorable Hodgkin lymphoma: results of a prospective, multicenter double-step phase II study by Fondazione Italiana Linfomi

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Abstract

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14–115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3–103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011–003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.

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Acknowledgements

Many thanks go to Samantha Pozzi, Gianluca Gaidano, Barbara Botto, Francesco Passamonti, Emanuele Angelucci, Roberto Freilone, Pier Paolo Fattori, Lucilla Tedeschi, Francesca Re, Annalia Molinari, and Carmine Selleri, who participated to the study. The reviewers of the PET/CT scans were Antonio Castagnoli, Eugenio Borsatti, Manjola Dona, Federica Elisei, Umberto Ficola, Marcello Rodari, and Mauro Sacchetti. The authors thank Luca Giacomelli, PhD, Ambra Corti, and Aashni Shah (Polistudium) for editorial assistance, funded by internal funds.

Author information

Author notes

  1. Michele Carella

    Present address: Clinica Villa Pia, Rome, Italy

  2. Andrea Gallamini

    Present address: Research and Clinical Innovation Department, Centre Antoine-Lacassagne, Nice, France

  3. Armando Santoro and Rita Mazza contributed equally to this work.

Authors and Affiliations

  1. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, Italy

    Armando Santoro & Carmelo Carlo-Stella

  2. IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy

    Armando Santoro, Rita Mazza, Francesca Ricci, Monica Balzarotti & Carmelo Carlo-Stella

  3. Medical Oncology Division, Centro Riferimento Oncologico, Aviano, Italy

    Michele Spina & Emanuela Chimienti

  4. Onco-Hematology Department, A. Tortora Hospital, Pagani, Salerno, Italy

    Catello Califano

  5. Emergency and Transplantation Department, Hematology Section, University of Bari Medical School, Bari, Italy

    Giorgina Specchia

  6. Hematology and Bone Marrow Transplantation Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Michele Carella & Chiara Ghiggi

  7. Clinica La Madonnina, Milan, Italy

    Michele Carella

  8. Hematology Department, Garibaldi Nesima Hospital, Catania, Italy

    Ugo Consoli

  9. Regina, Elena National Cancer Institute, Rome, Italy

    Francesca Palombi

  10. Onco-Hematology Unit, Casa Di Cura “La Maddalena”, Palermo, Italy

    Maurizio Musso

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

    Alessandro Pulsoni

  12. Hematology Department, AOU Careggi, Florence, Italy

    Sofya Kovalchuk

  13. Hematology Division, IRCCS Policlinico S. Matteo, Pavia, Italy

    Maurizio Bonfichi

  14. Hematology Unit, AOU Senese, Siena, Italy

    Alberto Fabbri

  15. Onco-Hematology Division, S. Maria Hospital, Università Degli Studi Di Perugia, Terni, Italy

    Anna Marina Liberati

  16. IRCCS Humanitas Clinical and Research Hospital, Department of Diagnostic Imaging, Via Manzoni 56, Milano, Rozzano, Italy

    Marcello Rodari

  17. Biostatistic Unit, Humanitas Clinical and Research Hospital, Rozzano, Milano, Italy

    Laura Giordano

  18. Division of Hematology, S. Croce E Carle Hospital, Cuneo, Italy

    Roberto Sorasio & Andrea Gallamini

  19. Radiation Oncology Unit, Azienda Unità Sanitaria Locale IRCCS Di Reggio Emilia, Reggio Emilia, Italy

    Patrizia Ciammella

  20. Oncology Department, Radiation Oncology, University of Torino, Torino, Italy

    Umberto Ricardi

  21. Medical Physics Department, S. Croce E Carle Hospital, Cuneo, Italy

    Stephane Chauvie

  22. Hematology Department, Azienda Unità Sanitaria Locale IRCCS Di Reggio Emilia, Reggio Emilia, Italy

    Francesco Merli

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  1. Armando Santoro
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  2. Rita Mazza
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Contributions

Conceptualization: AS, RM, and FM. Methodology: AS and RM. Formal analysis: LG. Investigation: All. Data curation: LG. Writing—original draft preparation: AS and RM. Writing—review and editing: All.

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Correspondence to Armando Santoro.

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Santoro, A., Mazza, R., Spina, M. et al. Dose-dense ABVD as first-line therapy in early-stage unfavorable Hodgkin lymphoma: results of a prospective, multicenter double-step phase II study by Fondazione Italiana Linfomi. Ann Hematol 100, 2547–2556 (2021). https://doi.org/10.1007/s00277-021-04604-x

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