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Is re-challenge still an option as salvage therapy in multiple myeloma? The case of REal-life BOrtezomib re-Use as secoND treatment for relapsed patients exposed frontline to bortezomib-based therapies (the REBOUND Study)

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Abstract

Therapeutic re-challenge is currently a debated issue in the field of multiple myeloma (MM), given the recent availability of several new drugs and combinations. However, very few specific evidences are available about bortezomib re-use at first relapse. This multicenter, observational, retrospective study enrolled 134 MM patients with significant response after bortezomib-based frontline regimens and who had received a first salvage treatment containing bortezomib at relapse. The overall response rate was 71%, including 40% partial responses, 24% very good partial responses, and 7% complete responses. Re-treatment was well-tolerated, with no significant new or unexpected toxicities observed. The median duration of second progression-free survival (PFS) was 15 months, while median PFS2 was 55 months. With a median follow-up of 56 months, overall survival was 94 months for the entire series, without significant differences between patients undergoing or not undergoing transplant procedures. This real-life survey indicates that re-treatment including bortezomib as a first salvage therapy could be still considered in MM patients achieving durable response after initial exposure to bortezomib.

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Funding

This study was supported by a dedicated donation from Janssen-Cilag Italy and by Current Research Funds 2016 from the Italian Ministry of Health to IRCCS-CROB.

Author information

Author notes

  1. Silvia Mangiacavalli and Alessandro Corso contributed equally to this work.

Authors and Affiliations

  1. Haematology and Stem Cell Transplantation Unit, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, PZ, Italy

    Pellegrino Musto, Oreste Villani, Giuseppe Pietrantuono, Giovanni D’Arena & Giovanna Mansueto

  2. Department of Public, Clinical and Preventive Medicine, Medical Statistics Unit, University of Campania Luigi Vanvitelli, Naples, Italy

    Vittorio Simeon

  3. Haematology and SCT Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy

    Nicola Cascavilla & Antonietta Falcone

  4. Haematology Unit, Department of Cellular Biotechnologies and Haematology, La Sapienza University, Rome, Italy

    Maria Teresa Petrucci & Laura Cesini

  5. Haematology Unit, Azienda Policlinico OVE, University of Catania, Catania, Italy

    Francesco Di Raimondo & Concetta Conticello

  6. Internal Medicine and Clinical Oncology, AOU Policlinico Giovanni XXIII, University of Bari, Bari, Italy

    Roberto Ria

  7. Haematology and SCT Unit, Federico II University, Naples, Italy

    Lucio Catalano & Dalila Salvatore

  8. Haematology Unit, S. Gennaro Hospital, Naples, Italy

    Lucia Mastrullo & Alfredo Gagliardi

  9. Haematology Unit, AOU Città della Salute e della Scienza, Turin, Italy

    Sara Bringhen, Mariella Genuardi & Mario Boccadoro

  10. Haematology and SCT Unit, Vito Fazzi Hospital, Lecce, Italy

    Nicola Di Renzo & Giovanni Reddiconto

  11. Haematology Unit, Madonna delle Grazie Hospital, Matera, Italy

    Alberto Fragasso

  12. Haematology Unit, S. Eugenio Hospital, Rome, Italy

    Tommaso Caravita

  13. Management Control Unit, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, PZ, Italy

    Daniele Scapicchio

  14. Scientific Direction, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, PZ, Italy

    Gioacchino Marziano

  15. Haematology Unit, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

    Silvia Mangiacavalli & Alessandro Corso

Authors
  1. Pellegrino Musto
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  2. Vittorio Simeon
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  4. Antonietta Falcone
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  5. Maria Teresa Petrucci
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  8. Concetta Conticello
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Contributions

PM designed the study and is the responsible for the concept of this manuscript; VS analyzed database and performed statistical analysis; NC, AF, MTP, LC, FDR, CC, RR, LC, DS, LM, AG, OV, GP, GD, GM, SB, MG, NDR, GR, AG, TC, and MB recruited patients and provided relevant data; DS and GM collected, assembled, and managed database; PM, SM, and AC coordinated the various authors and wrote the paper. All authors critically reviewed the manuscript drafts, approved the final version, and made the decision to submit the manuscript for publication.

Corresponding author

Correspondence to Pellegrino Musto.

Ethics declarations

After Local Ethic Committee approval, charts of 134 MM eligible patients treated in 12 Italian centers from January 2002 to May 2015 were reviewed. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Due to the restrospective, observational nature of the study and according to current Italian law, obligatory informed consent was not necessary from all patients for being included in the study. Bortezomib-based treatments were performed according to current clinical practice at local institutions.

Conflict of interest

Regarding possible COI with the present paper, PM has participated to Advisory Boards of and has received honoraria from Celgene, Janssen-Cilag, BMS, Amgen, and Takeda; MTP is a member of the Advisory Board and has received honoraria from Celgene, Janssen-Cilag, BMS, Amgen, and Takeda; RR is a member of the Advisory Board of Janssen-Cilag, Consultant for CSL Behring and Speakers bureau for Janssen-Cilag, Celgene, Italfarmaco, BMS, Amgen, and CSL Behring; TC is a member of the Advisory board of Janssen-Cilag, Celgene, BMS, Amgen, and Takeda and received research funds from Celgene; SB is a member of the Advisory Board of Janssen-Cilag, Amgen, and Takeda and received honoraria from Janssen and Cilag, Celgene, Amgen, and BMS; MB is a member of the Advisory Board and has received honoraria from Celgene, Janssen-Cilag, BMS, Amgen, and Takeda. Other authors did not declare any COI.

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Musto, P., Simeon, V., Cascavilla, N. et al. Is re-challenge still an option as salvage therapy in multiple myeloma? The case of REal-life BOrtezomib re-Use as secoND treatment for relapsed patients exposed frontline to bortezomib-based therapies (the REBOUND Study). Ann Hematol 98, 361–367 (2019). https://doi.org/10.1007/s00277-018-3524-1

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