Superior overall survival of patients with myeloma achieving very good partial response or better to initial treatment with bortezomib, pegylated liposomal doxorubicin, and dexamethasone, predicted after two cycles by a free light chain- and M-protein-based model: extended follow-up of a phase II trial

Abstract

In myeloma, achievement of very good partial response (VGPR) post-transplant is associated with prolonged overall (OS) and progression-free survival (PFS). In this study of bortezomib, pegylated liposomal doxorubicin, and dexamethasone (VDD) in 40 patients with newly diagnosed myeloma (median follow-up 45.1 months), 2-/4-year OS estimates were 95.7%/86.5% versus 82.4%/58.2% for patients achieving ≥VGPR versus <VGPR to VDD (p=0.0241). In 30 patients undergoing transplant, PFS (p = 0.0357) and OS (p = 0.0272) were longer in patients achieving ≥VGPR to VDD. Achievement of ≥VGPR was predicted by a novel model based on occurrence after two cycles of ≥90% involved free light chain reduction, free light kappa/lambda ratio normalization, and/or ≥90% M-protein reduction. Prediction of ≥VGPR was associated with superior PFS and OS in patients with transplant. These findings emphasize the importance of achieving ≥VGPR to initial therapy, associated with prolonged OS. The predictive model provides a potential basis for developing individualized therapy, which requires further study.

Keywords:

• Outcome prediction
• free light chain
• M-protein
• very good partial response
• survival
• myeloma

Acknowledgments

The authors acknowledge the editorial assistance of Steve Hill, a medical writer with FireKite, in finalizing the manuscript for submission. This assistance was supported by Millennium Pharmaceuticals, Inc. We would also like to thank Stephen J. Harding, from The Binding Site, Ltd, for reviewing the manuscript.

A.J.J. is a consultant for Millennium Pharmaceuticals, Inc. and Onyx Pharmaceuticals, served as a consultant for Celgene and Ortho Biotech, and served on Speakers Bureaus for Millennium Pharmaceuticals, Inc., Ortho Biotech, and Celgene; all activities are unpaid as of August 2010. All other authors declare no competing financial interests.

Potential conflict of interest:

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