Bortezomib-containing induction regimens in transplant-eligible myeloma patients

A meta-analysis of phase 3 randomized clinical trials

Authors

  • Ajay K. Nooka MD, MPH,

    1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Jonathan L. Kaufman MD,

    1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Madhusmita Behera PhD,

    1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Amelia Langston MD,

    1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Edmund K. Waller MD, PhD,

    1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Christopher R. Flowers MD, MS,

    1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Charise Gleason NP,

    1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Lawrence H. Boise PhD,

    1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Sagar Lonial MD

    Corresponding author
    1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia
    • Corresponding author: Sagar Lonial, MD, Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, 1365 Clifton Road NE, C4004, Atlanta, GA 30322; Fax: (404) 778-5530; sloni01@emory.edu

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  • Presented in abstract form at the 53rd Annual Meeting of the American Society of Hematology; December 10-13, 2011; San Diego, California.

Abstract

BACKGROUND

The objective of this meta-analysis in patients with myeloma was to test the hypothesis that the addition of bortezomib to induction therapy not only improves the depth of response but also improves post-transplant progression-free survival (PFS) and overall survival (OS) outcomes.

METHODS

Phase 3 trials that randomized newly diagnosed, transplant-eligible patients with myeloma to receive either a bortezomib-containing induction regimen (BCIR) or a nonbortezomib-containing induction regimen (NBCIR) were identified. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adapted for data synthesis, and comprehensive meta-analysis software was used to report pooled data as hazard ratios or odds ratios under a random-effects model.

RESULTS

Four published phase 3 trials that included 2169 patients were analyzed. The postinduction and post-transplant pooled odds ratio for achieving a complete response/near complete response or a very good partial response or better and the overall response rate were higher with BCIR. The pooled hazard ratios for 3-year PFS and OS were 0.71 (95% confidence interval, 0.60-0.83; P < .00,001) and 0.79 (95% confidence interval, 0.66-0.96; P = .014), respectively, favoring BCIR. The odds of developing selected grade ≥3 toxicities (peripheral neuropathy and varicella-zoster virus reactivation) also were higher with BCIR.

CONCLUSIONS

The current meta-analysis demonstrated that BCIR results in an improved depth of response, which translates into improved post-transplant PFS and OS outcomes despite a higher incidence of toxicity. This analysis supports the concept that the choice of induction regimen can influence post-transplant outcomes such as PFS and OS. Cancer 2013;119:4119–4128. © 2013 American Cancer Society.

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