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Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation

Bone Marrow Transplantation volume 55, pages 1810–1816 (2020)Cite this article

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Abstract

Contrary to tandem autologous transplant (auto-auto), autologous followed by reduced intensity conditioning allogenic transplantation (auto-allo) offers graft-versus-myeloma (GVM) effect but with higher toxicity. Trials comparing these two strategies relied on availability of HLA-matched sibling donors for arm allocation (biological randomization) and yielded conflicting results. A pooled analysis of multiple trials with extended follow up provides an opportunity to compare these strategies. We obtained individual patient data from participants of four trials comparing auto-auto vs. auto-allo after induction therapy. There were 899 patients in auto-auto and 439 in auto-allo. Median follow up of survivors was 118.5 months. Median overall survival (OS) was 78.0 months in auto-auto and 98.3 months in auto-allo (HR = 0.84, P = 0.02). OS was 36.4% vs. 44.1% at 10 years (P = 0.01) for auto-auto and auto-allo, respectively. Progression-free survival was also improved in auto-allo (HR = 0.84, P = 0.004). Risk of non-relapse mortality was higher in auto-allo (10 year 8.3% vs. 19.7%, P < 0.001), while risk of disease progression was higher in auto-auto (10 year 77.2% vs. 61.6%, P < 0.001). Median post relapse survival was 41.5 months in auto-auto and 62.3 months in auto-allo (HR = 0.71, P < 0.001). This supports the existence of durable GVM effect enhancing myeloma control with subsequent therapies.

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Fig. 1: Outcomes of the comprehensive search strategy.
Fig. 2: Risks of relapse and non-relapse mortality.
Fig. 3: Long term outcomes per transplant strategy.
Fig. 4: Post relapse survival.

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Acknowledgements

This work was presented as an oral abstract at the 61st Annual Meeting of the American Society of Hematology, Orlando, FL, USA, December 7–10, 2019. This study was not funded commercially. Support for this study was provided to the Blood and Marrow Transplant Clinical Trials Network by grant #U01HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute, along with funding from the Southwest Oncology Group (SWOG grant award U10CA180888). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or SWOG.

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Authors and Affiliations

  1. University of Alabama at Birmingham, Birmingham, AL, USA

    Luciano J. Costa, Riddhi Modi & Elizabeth E. Brown

  2. Rome University Tor Vergata, Rome, Italy

    Simona Iacobelli

  3. CIBMTR and Medical College of Wisconsin, Milwaukee, WI, USA

    Marcelo C. Pasquini & Parameswaran Hari

  4. University of Torino, Torino, Italy

    Luisa Giaccone & Benedetto Bruno

  5. University of Barcelona, Barcelona, Spain

    Joan Blade

  6. University Hospital Heidelberg, Heidelberg, Germany

    Stefan Schonland

  7. Citt Della Salute E Della Scienza, Torino, Italy

    Andrea Evangelista

  8. Universidad de Sevilla, Sevilla, Spain

    Jose A. Perez-Simon

  9. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Sergio A. Giralt

  10. University of Udine, Udine, Italy

    Francesca Patriarca

  11. University of Pennsylvania, Philadelphia, PA, USA

    Edward A. Stadtmauer

  12. Josep Carreras Research Institute, Barcelona, Spain

    Laura Rosinol

  13. City of Hope Medical Center, Duarte, CA, USA

    Amrita Y. Krishnan

  14. Karolinska University Hospital, Stockholm, Sweden

    Gösta Gahrton

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  1. Luciano J. Costa
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Correspondence to Luciano J. Costa.

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Conflict of interest

LJC: Consultancy (Karyopharm, Celgene, Amgen, Sanofi, Abbvie, GSK), Research Funding (Amgen, Janssen); Honoraria (Celgene, Janssen, Amgen). MCP Consultancy (Pfizer, Medigene, Amgen, Novartis), Research Funding (Kite Pharmaceuticals, BMS). JB: Advisory committee (Janssen, Celgene, Amgen, Takeda). SS Research Funding (Prothena, Takeda, Janssen), Honoraria (Prothena, Medac, Janssen). PH: Consultancy (Celgene, Takeda, BMS, Janssen, Kite Pharmaceuticals, Amgen, Spectrum, Abbvie), Honoraria (Celgene, Takeda, Janssen, Kite Pharmaceuticals, Sanofi, Abbvie), Research Funding (Celgene, Takeda, BMS, Kite Pharmaceuticals, Spectrum). SAG: Consultancy (Jazz Pharmaceuticals, Novartis, Takeda, Celgene, Kite Pharmaceuticals, Johnson & Johnson, Actinium, Amgen, Spectrum Pharmaceuticals), Research Funding (Takeda, Celgene, Johnson & Johnson, Actinium, Miltenyi, Amgen). FP: Membership on Advisory Committee (Takeda, Celgene, Janssen). AYK: Consultancy (Abbvie, Novartis, Celgene, Takeda), Research Funding (Abbvie, Novartis, Tmunity). GG: Consultancy (Fujimoto Pharmaceutical Corporation). The remaining authors declare that they have no conflict of interest.

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Costa, L.J., Iacobelli, S., Pasquini, M.C. et al. Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation. Bone Marrow Transplant 55, 1810–1816 (2020). https://doi.org/10.1038/s41409-020-0887-4

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