Journal of Cancer Research and Clinical Oncology

, Volume 144, Issue 7, pp 1357–1366 | Cite as

Maintenance in myeloma patients achieving complete response after upfront therapy: a pooled analysis

  • Chiara Cerrato
  • Francesco Di Raimondo
  • Lorenzo De Paoli
  • Stefano Spada
  • Francesca Patriarca
  • Claudia Crippa
  • Roberto Mina
  • Tommasina Guglielmelli
  • Dina Ben-Yehuda
  • Daniela Oddolo
  • Chiara Nozzoli
  • Emanuele Angelucci
  • Nicola Cascavilla
  • Rita Rizzi
  • Stefano Rocco
  • Luca Baldini
  • Elena Ponticelli
  • Magda Marcatti
  • Clotilde Cangialosi
  • Tommaso Caravita
  • Giulia Benevolo
  • Roberto Ria
  • Arnon Nagler
  • Pellegrino Musto
  • Paola Tacchetti
  • Paolo Corradini
  • Massimo Offidani
  • Antonio Palumbo
  • Maria Teresa Petrucci
  • Mario Boccadoro
  • Francesca Gay
Original Article – Clinical Oncology
  • 242 Downloads

Abstract

Purpose

Maintenance demonstrated to improve survival in newly diagnosed multiple myeloma (NDMM) patients and the achievement of complete response (CR) is a strong predictor of survival. Nevertheless, the role of maintenance according to response after induction/consolidation has not been investigated so far. To evaluate the impact of maintenance according to response, we pooled together and retrospectively analyzed data from 955 NDMM patients enrolled in two trials (GIMEMA-MM-03-05 and RV-MM-PI-209).

Methods

Primary endpoints were progression-free survival (PFS)1, PFS2 and overall survival (OS) of CR patients randomized to maintenance and no maintenance. Secondary endpoints were PFS1, PFS2 and OS in very good partial response/partial response (VGPR/PR) patients.

Results

Overall, 213 patients obtained CR after induction/consolidation, 118 received maintenance and 95 no maintenance. In patients achieving CR, maintenance significantly improved PFS1 (HR 0.50, P < 0.001), PFS2 (HR 0.58, P 0.02) and OS (HR 0.51, P 0.02) compared with no maintenance; the advantage was maintained across all the analyzed subgroups according to age, International Staging System (ISS) stage, cytogenetic profile and treatment. Similar features were seen in VGPR/PR patients.

Conclusion

Maintenance prolonged survival in CR and in VGPR/PR patients. The benefit in CR patients suggests the importance of continuing treatment in patients with chemo-sensitive disease.

Trial registration

The two source studies are registered at ClinicalTrials.gov: identification numbers NCT01063179 and NCT00551928.

Keywords

Multiple myeloma (MM) Maintenance therapy Newly diagnosed Complete response (CR) Prognosis 

Notes

Acknowledgements

The authors thank the patients who participated in the source trials, the nurses Manuela Grasso and Luca Merlone, the data managers Jessica Mastrovito and Elena Tigano, the editorial assistants Giorgio Schirripa and Ugo Panzani.

Compliance with ethical standards

Conflict of interest

FDR has received honoraria from Celgene, BMS, and Janssen; FP has received honoraria from Celgene, Janssen, BMS; CN has served on the Advisory Board for Celgene; TC has received consultancy fees from Takeda and served on the advisory board for Jannsen, Celgene, BMS, Amgen; PM has received Honoraria from Janssen-Cilag and Celgene; PC has received honoraria from Celgene; MO has received honoraria from Celgene; AP is currently a Takeda employee; MTP has received honoraria from Celgene, Janssen-Cilag, BMS, Amgen, Takeda; MB has received research funding from Amgen, BMS, Celgene, Janssen, Mundipharma, Novartis, Sanofi; and honoraria from AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Sanofi. FG has served on the advisory board for Takeda, Seattle Genetics, Roche, Mundipharma, Janssen; and received honoraria from Takeda, Amgen, Celgene, Janssen, BMS. All the other authors have no potential conflicts of interest.

Ethical approval

GIMEMA-MM-03-05 and RV-MM-PI-209 source studies were approved by the ethics committee of the coordinating site A.O.U. Città della Salute e della Scienza di Torino (Torino, Italy): Comitato Etico Interaziendale A.O.U. Città della Salute e della Scienza di Torino—A.O. Ordine Mauriziano—ASL Città di Torino. All procedures performed in both source 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.

Informed consent

Informed consent was obtained from all individual participants included in both source studies.

Supplementary material

432_2018_2641_MOESM1_ESM.pdf (805 kb)
Supplementary material 1 (PDF 804 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Chiara Cerrato
    • 1
  • Francesco Di Raimondo
    • 2
  • Lorenzo De Paoli
    • 3
  • Stefano Spada
    • 1
  • Francesca Patriarca
    • 4
  • Claudia Crippa
    • 5
  • Roberto Mina
    • 1
  • Tommasina Guglielmelli
    • 6
  • Dina Ben-Yehuda
    • 7
  • Daniela Oddolo
    • 1
  • Chiara Nozzoli
    • 8
  • Emanuele Angelucci
    • 9
  • Nicola Cascavilla
    • 10
  • Rita Rizzi
    • 11
  • Stefano Rocco
    • 12
  • Luca Baldini
    • 13
  • Elena Ponticelli
    • 1
  • Magda Marcatti
    • 14
  • Clotilde Cangialosi
    • 15
  • Tommaso Caravita
    • 16
  • Giulia Benevolo
    • 17
  • Roberto Ria
    • 18
  • Arnon Nagler
    • 19
  • Pellegrino Musto
    • 20
  • Paola Tacchetti
    • 21
  • Paolo Corradini
    • 22
  • Massimo Offidani
    • 23
  • Antonio Palumbo
    • 1
    • 25
  • Maria Teresa Petrucci
    • 24
  • Mario Boccadoro
    • 1
  • Francesca Gay
    • 1
  1. 1.Myeloma Unit, Division of HematologyUniversity of Torino, Azienda-Ospedaliero Universitaria Città della Salute e della Scienza di TorinoTorinoItaly
  2. 2.UOC EmatologiaAzienda Policlinico-OVE, University of CataniaCataniaItaly
  3. 3.Division of Hematology, Department of Translational MedicineUniversity of Eastern Piedmont and Maggiore HospitalNovaraItaly
  4. 4.Dipartimento di MedicinaUniversità di UdineUdineItaly
  5. 5.Divisione di EmatologiaSpedali Civili BresciaBresciaItaly
  6. 6.Department of Clinical and Biological SciencesOrbassanoItaly
  7. 7.Hematology Department, Hadassah Medical CenterJerusalemIsrael
  8. 8.SODc Terapie cellulari e medicina trasfusionale AOUC CareggiFirenzeItaly
  9. 9.IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul CancroGenovaItaly
  10. 10.Hematology “Casa Sollievo della Sofferenza” Hospital IRCCSSan Giovanni RotondoItaly
  11. 11.Section of Hematology with Transplantation, Department of Emergency and Organ TransplantationUniversity of Bari Medical SchoolBariItaly
  12. 12.UOSC Ematologia con Trapianto - AORN Cardarelli NapoliNapoliItaly
  13. 13.Department of Oncology and Hemato-oncologyUniversity of Milan, Fondazione IRCCS Cà Granda, Ospedale Maggiore PoliclinicoMilanoItaly
  14. 14.U.O. Ematologia e Trapianto di MidolloIRCCS Ospedale San RaffaeleMilanoItaly
  15. 15.Ospedali Riuniti Villa Sofia-Cervello, Unità Operativa di Ematologia I e UTMOPalermoItaly
  16. 16.UOC Ematologia Ospedale S. Eugenio ASL RM2RomaItaly
  17. 17.SC HematologyCittà della Salute e della Scienza HospitalTorinoItaly
  18. 18.University of Bari “Aldo Moro” Medical School, Department of Biomedical Science, Internal Medicine “G. Baccelli”, PoliclinicoBariItaly
  19. 19.Hematology Division, Chaim Sheba Medical CenterTel HaShomerRamat GanIsrael
  20. 20.Scientific DirectionIRCCS Referral Cancer Center of BasilicataRionero in VultureItaly
  21. 21.“Seràgnoli” Institute of Hematology, Department of Experimental, Diagnostic and Specialty MedicineBologna University School of MedicineBolognaItaly
  22. 22.Department of Oncology and HematologyUniversity of MilanoMilanoItaly
  23. 23.Clinica di EmatologiaAOU Ospedali Riuniti di AnconaLoc. Torrette, AnconaItaly
  24. 24.Hematology“Sapienza” University of RomeRomaItaly
  25. 25.TakedaZürichSwitzerland

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