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First-line therapy for non-transplant eligible patients with multiple myeloma: direct and adjusted indirect comparison of treatment regimens on the existing market in Germany

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Abstract

Objectives

The purpose of this study was to compare approved first-line therapies for patients with multiple myeloma.

Methods

A systematic literature search for phase III randomized controlled trials (RCTs) comparing first-line chemotherapies approved in Germany and recommended by guidelines at the time of study design was conducted. Random-effects meta-analysis (MA) was used for direct and the Bucher method for adjusted indirect treatment comparison.

Results

One RCT comparing melphalan and prednisone plus bortezomib (VMP) vs. melphalan and prednisone (MP) and six RCTs comparing MP plus thalidomide (MPT) vs. MP were analysed. For MPT vs. MP, an individual patient data (IPD) MA was used for sensitivity analyses. VMP and MPT were superior to MP regarding efficacy endpoints (VMP vs. MP, overall survival (OS): hazard ratio (HR) 0.70, 95 % confidence interval (CI) 0.57–0.86; progression-free survival (PFS): HR 0.56, 0.39–0.79; complete response (CR), risk-ratio (RR) for non-response: 0.70, 0.65–0.75; MPT vs. MP, OS: HR 0.83, 0.66–1.03; PFS: HR 0.67, 0.56–0.81; CR, RR for non-response 0.92, 0.88–0.95); but had a higher risk of developing any grade 3–4 adverse events (AEs) (VMP vs. MP: RR 1.13, 1.06–1.20; MPT vs. MP: RR 2.06, 1.43–2.98). The indirect comparison of VMP vs. MPT via MP showed a statistically not significant advantage for VMP regarding survival outcomes (OS: HR 0.85, 0.63–1.14; PFS: HR 0.83, 0.56–1.23) and a significant advantage regarding CR (RR for non-response 0.76, 0.70–0.83) and AEs (RR 0.55, 0.38–0.80). Treatment comparisons using results of IPD MA yielded similar effect sizes.

Conclusions

VMP and MPT seem more effective than MP, VMP was superior to MPT regarding response criteria and AEs. Our results may best be confirmed by a head-to-head trial of VMP vs. MPT.

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Authors’ contributions

KK, DW, MH and WL made substantial contributions to conception and design of this work. KS performed the initial systematic literature research, KK and DW updated it and selected relevant studies. KK and MH extracted data using results of KS and the original publications of eligible studies. KK and MH did the analysis, and DW and WL took part in the interpretation of the analysis. KK and DW drafted the manuscript. All authors made substantial contributions to creation of the final manuscript and revised the final draft of the manuscript critically for important intellectual content. All authors gave final approval of the version to be published.

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Authors and Affiliations

  1. Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, 50924, Koeln, Germany

    Kathrin Kuhr, Walter Lehmacher & Martin Hellmich

  2. Janssen-Cilag GmbH, Neuss, Germany

    Daniel Wirth

  3. HERON Health Pvt. Ltd, Chandigarh, India

    Kunal Srivastava

  4. BresMed Health Solutions India Pvt. Ltd, Malbhat, Margao, India

    Kunal Srivastava

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  1. Kathrin Kuhr
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Correspondence to Kathrin Kuhr.

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Funding

This study was funded by Janssen-Cilag GmbH, Neuss, Germany.

Conflicts of interest

KK and MH report grants from Janssen-Cilag, during the conduct of the study. WL reports grants from Janssen-Cilag, during the conduct of the study; personal fees from Janssen-Cilag for statistical courses, outside the submitted work. DW states being an employee of Janssen-Cilag. KS was working with HERON Health Pvt. Ltd., during the conduct of the study. HERON is a consultancy which was hired to conduct systematic reviews by Janssen. KS now works with BresMed Health Solutions. No other relationships or activities that may appear to have influenced the submitted work are declared.

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Kuhr, K., Wirth, D., Srivastava, K. et al. First-line therapy for non-transplant eligible patients with multiple myeloma: direct and adjusted indirect comparison of treatment regimens on the existing market in Germany. Eur J Clin Pharmacol 72, 257–265 (2016). https://doi.org/10.1007/s00228-015-1998-5

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