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Panobinostat Plus Bortezomib Versus Lenalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Treatment Comparison of Survival Outcomes using Patient-level Data

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Abstract

Background

In the UK, the standard of care for patients with multiple myeloma who received ≥2 prior treatments is lenalidomide plus dexamethasone (LEN + DEX) and pomalidomide plus DEX (POM + DEX) (in Wales only). Recently, panobinostat plus bortezomib and DEX (PAN + BTZ + DEX) was licensed in this setting. The current study assessed the progression-free survival (PFS) and overall survival (OS) outcomes with PAN + BTZ + DEX versus LEN + DEX (primary comparator) and POM + DEX (exploratory comparator).

Methods

Since an anchor-based indirect treatment comparison was not feasible, the matching-adjusted indirect treatment comparison approach was used. To compare the survival outcomes, patient-level data were generated for the comparators utilizing published Kaplan–Meier survival estimates. The use of approximated patient-level data and matched data for PAN + BTZ + DEX allowed the use of Cox proportional hazards models and the assessment of the proportional hazards assumption. In cases where there was evidence that the proportional hazards assumption was violated, time-dependent hazard ratios (HRs) were estimated. Median and mean values for PFS and OS were predicted.

Results

For both PFS and OS, the proportional hazards assumption was not satisfied, therefore time-dependent HRs were estimated. Using time-dependent HRs, the mean PFS was estimated to be 11.83 months for PAN + BTZ + DEX and 10.96 months for LEN + DEX. The corresponding mean OS estimates were 30.73 and 27.76 months, respectively. Comparisons with POM + DEX were affected by large uncertainty and did not allow making robust inferences.

Conclusions

To our knowledge, this is the first study that combined matching-adjusted indirect treatment comparison with time-dependent HRs to address changing patterns in the HR. The results suggest that treatment with PAN + BTZ + DEX and LEN + DEX are associated with similar mean PFS and OS in the third-line treatment setting of multiple myeloma.

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Author contributions

IMM, GvdW and ZP contributed to the conception of the study. IMM performed the analyses. All authors contributed to the writing of the manuscript and gave final approval of the version to be submitted.

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Authors and Affiliations

  1. Pharmerit International, Health Economics and Outcomes Research, Marten Meesweg 107, 3068 AV, Rotterdam, The Netherlands

    Istvan Majer & Gijs van de Wetering

  2. Novartis Pharmaceuticals UK, Surrey, UK

    Zoltan Polanyi, Arun Krishna & Elisabeth Gray

  3. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    Anuja Roy

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  1. Istvan Majer
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Corresponding author

Correspondence to Gijs van de Wetering.

Ethics declarations

Declaration of funding: Financial support for this study was provided by a Grant from Novartis. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. The following authors are employed by the sponsor: A. Roy, A. Krishna, E. Gray, and Z. Polanyi. IMM, and GvdW are employees of Pharmerit International, who were paid consultants to Novartis for performing this research. IMM and GvdW have no conflict of interest to report. The authors attest that any and all financial or other relationships, including financial support of the study that could be construed as a conflict of interest, have been disclosed in the acknowledgements. All authors have read and approved the final draft of the manuscript.

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Majer, I., van de Wetering, G., Polanyi, Z. et al. Panobinostat Plus Bortezomib Versus Lenalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma: A Matching-Adjusted Indirect Treatment Comparison of Survival Outcomes using Patient-level Data. Appl Health Econ Health Policy 15, 45–55 (2017). https://doi.org/10.1007/s40258-016-0271-0

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