Continuous induction with lenalidomide/dexamethasone versus autologous stem cell transplantation in newly diagnosed multiple myeloma: a case for response-adapted approach

Abstract

Although upfront autologous stem cell transplantation (ASCT) generally improves progression-free survival (PFS) in newly diagnosed multiple myeloma (NDMM), the overall survival (OS) benefit and optimal timing of ASCT are not well established. Patients with early response may be able to safely continue induction and avoid ASCT without compromised outcomes. We report an extended follow-up analysis of a phase 2 trial that randomized transplant-eligible patients with NDMM who responded to induction (50/65 patients) to continued induction or ASCT; median follow-up was 8.0 years. Patients had similar 8-year PFS (55% vs. 43%), 8-year OS (83% vs. 72%), and rates of at least very good partial response (72% vs. 84%) whether continuing induction of lenalidomide and dexamethasone (Ld arm) or receiving ASCT (Ld + ASCT arm) (p = 0.5). Notably, over 50% of patients receiving continuous Ld had PFS of 5–10 years. These results suggest the need for prospective trials incorporating response-adapted therapeutic approaches to NDMM.

STATEMENT OF PRIOR PRESENTATION

• Presented in abstract form (interim analysis) at the 56th annual meeting of the American Society of Hematology (San Francisco, CA, 6 December 2014) and at the 57th annual meeting of the American Society of Hematology (Orlando, FL, 3 December 2015).

Keywords:

• Multiple myeloma
• stem cell transplantation
• lenalidomide
• continuous induction
• response-adapted therapy

Acknowledgments

Editorial support in the preparation of the manuscript was provided by the Memorial Sloan Kettering Cancer Center Editorial Service, Hannah Rice, BA, ELS, and Crystal Tran, BS.

Author contributions

H.H., R.L.C., H.L., S.D., designed the research; H.H, H.L., O.L, N.L., J.N., J.W., A.M.L., T.K., S.G., S.M, N.K. and O.C.L. performed the research; H.H, O.L, H.L, S.D., J.W., J.N. and O.C.L. analyzed the data; H.H, O.L, H.L, and R.L.C., wrote the manuscript; H.H, O.L, H.L, J.N., J.W., and T.A. contributed to data collection; H.H. O.L. H.L, N.K., N.L., T.K., A.M.L., S.M., S.G., and R.L.C. enrolled patients and assisted with their care; all authors critically reviewed and approved the submission of this manuscript.

Disclosure statement

H.H. received consultancy fees and honoraria from Novartis; received research funding from Celgene and Takeda Pharmaceuticals; and served on the advisory committee for Takeda Pharmaceuticals. O.L. served on the advisory board for MorphoSys AG. H.L. served on the advisory committee for Takeda Pharmaceuticals, Celgene, Janssen Pharmaceuticals, Sanofi, and Caelum Biosciences; received honorarium from Sanofi; and received research funding from Takeda Pharmaceuticals. T.K. received consultancy fees from Juno Pharmaceuticals Inc., Gilead Sciences, Inc., Concert Pharmaceuticals Inc., and AbbVie, Inc. C.O.L. received consultancy fees from Amgen Inc., Merck & Co., Inc., Millennium Pharmaceuticals, Inc. (acquired by Takeda Pharmaceuticals in 2008), Onyx Pharmaceuticals, Inc. (acquired by Amgen in 2013), and Takeda Pharmaceuticals. The remaining authors declare no competing financial interests that might benefit from this publication.

Additional information

Funding

The reported research was supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) Memorial Sloan Kettering Cancer Center Support Grant [P30 CA008748]. Medical writing support in the preparation of this manuscript was provided by Sandralee Lewis, PhD, on behalf of the Investigator Initiated Research Writing Group (an initiative from Ashfield Healthcare, a part of UDG Healthcare plc), and was funded by Celgene Corporation.