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Multiple Myeloma, Gammopathies

Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis

Leukemia volume 31, pages 1727–1734 (2017)Cite this article

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Abstract

In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200 mg/m2 and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.

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Acknowledgements

We thank all the patients who participated in the source studies; the Australasian Leukaemia and Lymphoma Group (ALLG); the nurses Luisella D’Ambrosio and Tiziana De Lazzer, the data managers Marta Santoro and Federica Leotta, and the editorial assistant Giorgio Schirripa from Torino site. The RV-MM-PI-209 and the EMN-441 studies were sponsored by Fondazione Neoplasie Sangue Onlus and supported by Celgene. The funder of the source studies had no role in the present study, and no funding was received for this analysis.

Author contributions

FG, AP and MB designed the study; FG and AP collected and assembled the data; FG, AE, SS, MS, AP and MB analyzed and interpreted the data; FG wrote the first draft of the manuscript; all authors had access to the final data and approved the final manuscript.

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Author notes

  1. A Palumbo: Currently Takeda Pharmaceutical employee.

Authors and Affiliations

  1. Division of Hematology, Myeloma Unit, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy

    F Gay, S Oliva, S Spada, M Salvini, P Omedé, R Troia, A Malfitano, A Palumbo & M Boccadoro

  2. Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Roma, Roma, Italy

    M T Petrucci

  3. Department of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

    V Montefusco

  4. Division of Hematology, Azienda Policlinico 'Vittorio Emanuele', University of Catania, Catania, Italy

    C Conticello

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

    P Musto

  6. Department of Clinical Medicine and Surgery, Hematology, AOU Federico II, Napoli, Italy

    L Catalano

  7. Unit of Clinical Epidemiology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino and CPO Piemonte, Torino, Italy

    A Evangelista

  8. Haematology Department, Cancer Services, Barwon Health, Geelong, Australia

    P Campbell

  9. Department of Biomedical Science, University of Bari 'Aldo Moro' Medical School, Internal Medicine 'G. Baccelli' Policlinico, Bari, Italy

    R Ria

  10. Hematology Department, AOU Ospedali Riuniti di Ancona, Ancona, Italy

    M Offidani

  11. Hematology and Bone Marrow Transplantation Unit, IRCCS San Martino-Ist, Genova, Italy

    A M Carella

  12. Department of Oncohematology, AO S.Maria di Terni, Terni, Italy

    A M Liberati

  13. Division of Hematology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy

    A M Cafro

  14. Division of Hematology, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy

    A P Falcone

  15. UOC Ematologia S. Eugenio ASL RM2 Roma, Roma, Italy

    T Caravita

  16. Department of Hematology, Azienda Ospedaliera-Universitaria di Udine, DISM, Università di Udine, Udine, Italy

    F Patriarca

  17. Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel

    A Nagler

  18. Department of Clinical Haematology, Alfred Health-Monash University, Melbourne, Australia

    A Spencer

  19. Department of Haematooncology, Blood Cancer Research Group, Faculty Hospital Ostrava, Ostrava, Czech Republic

    R Hajek

  20. Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic

    R Hajek

Authors
  1. F Gay
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  2. S Oliva
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  3. M T Petrucci
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  21. T Caravita
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  25. R Hajek
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  26. A Palumbo
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Corresponding author

Correspondence to F Gay.

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Competing interests

FG has received honoraria from Amgen, BMS, Celgene and Takeda, and served on the advisory committee for Janssen, Mundipharma, and Takeda. SO has received honoraria from Takeda and Celgene. MTP has received honoraria from Celgene, Janssen-Cilag, Bristol-Myers Squibb, Amgen, Takeda, Mundipharma, Sanofi. PM has received honoraria from Celgene, Janssen, Novartis, Sanofi, Bristol-Myers Squibb, Takeda, Amgen. MO has received honoraria from Celgene. TC has received honoraria from Celgene, Janssen, Amgen, Bristol-Myers Squibb, and consultancy fees from Takeda. FP has received honoraria from MSD Italia, Celgene, and served on the advisory board of Janssen, Mundipharma, Amgen, Bristol-Meyers Squibb. AS has received honoraria from Celgene. RH has received consultancy fees from Celgene, Janssen, and honoraria from Amgen. AP has received consultancy fees, honoraria and research funding from Celgene, and is a Takeda employee. MB has received consultancy fees from Janssen, Sanofi, Onyx, Amgen, Celgene. The remaining authors declare no conflict of interest.

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Gay, F., Oliva, S., Petrucci, M. et al. Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis. Leukemia 31, 1727–1734 (2017). https://doi.org/10.1038/leu.2016.381

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