Real-world long-term outcomes in multiple myeloma with VRD induction, Mel200-conditioned auto-HCT, and lenalidomide maintenance

Abstract

Standard-of-care for newly-diagnosed, autologous hematopoietic stem cell transplantation (auto-HCT)-eligible, multiple myeloma (MM) patients includes bortezomib, lenalidomide, and dexamethasone (VRD) induction followed by melphalan 200 mg/m² (Mel200)-conditioned auto-HCT and lenalidomide maintenance. We completed a retrospective case series assessing outcomes of 187 MM patients who received this regimen at our institution. The 100-day non-relapse mortality incidence was zero. Before auto-HCT, 9.6 and 52.9% of patients achieved a complete response (CR) or ≥ very good partial response (VGPR), respectively. At day-100 post-transplant, 29.4 and 74.9% had achieved a CR/stringent-CR (sCR) or ≥ VGPR, respectively. At the last evaluation, 57.2% of patients had CR/sCR and 87.1% had ≥ VGPR. Median follow-up, progression-free survival (PFS), and overall survival (OS) were 63.2, 50, and 101.7 months, respectively. The 5-year PFS and OS were 43.1 and 79%. High-risk cytogenetics was associated with worse outcomes. This study illustrates that VRD induction, Mel200-conditioned auto-HCT, and lenalidomide maintenance are associated with good outcomes in MM.

Keywords:

• Multiple myeloma
• transplantation
• VRD
• lenalidomide
• outcomes
• Mel200

Acknowledgments

The authors would like to thank Mark Tanner, Ph.D. for the scientific editing of this manuscript.

Ethical approval

This retrospective case series was completed following approval by the MD Anderson Institutional Review Board and in accordance with the Declaration of Helsinki and the 1996 Health Insurance Portability and Accountability Act guidelines.

Author contributions

Mahmoud R. Gaballa: project development, data preparation, data interpretation, and manuscript writing. Junsheng Ma: statistical analysis, interpretation, and manuscript writing. Mark Tanner: scientific editing of the manuscript. Taha Al-Juhaishi, Qaiser Bashir, Samer A. Srour, Neeraj Saini, Jeremy Ramdial, Yago Nieto, Regan Murphy, Katy Rezvani, Guilin Tang, Hans Lee, Krina Patel, Gregory Kaufman, Elisabet E. Manasanch, Muhammad R. Ullah, Partow Kebriaei, Sheeba Thomas, Donna Weber, Robert Z. Orlowski, Elizabeth J. Shpall, and Richard Champlin: Critical review of the manuscript and editing the final draft. Muzaffar H. Qazilbash: project development, supervision, study design, interpretation of data, and manuscript writing.

Disclosure statement

Mahmoud Gaballa, Junsheng Ma, Mark Tanner, Taha Al-Juhaishi, Samer Srour, Neeraj Saini, Jeremy Ramdial, Regan Murphy, Guilin Tang, Muhammad R. Ullah, Donna Weber, and Richard E. Champlin: no conflicts of interest. Qaiser Bashir: research funding from Stemline, Acrotech, and Takeda. Advisory board for Takeda, Purdue, Amgen, and KITE. Consultancy for Stemline. Yago Nieto: grant support from Affimed, Novartis, Astra Zeneca, and Secura Bio. Consultancy for Affimed. Katy Rezvani: grant support from Affimed and Pharmacyclics. Personal fees from GemoAb and Virogen. A license and research agreement from Takeda Pharmaceuticals (outside the submitted work). A patent licensed (Development of CB‐CAR NK cells for the treatment of B‐cell malignancies and other cancers), with royalties paid to Takeda Pharmaceuticals. Advisory board of Gemoab, AvengeBio, Virogin, GSK, Bayer, and Navan Technologies. Hans C Lee: consultancy and research funding from Amgen, Celgene, Janssen, Takeda, and GlaxosmithKline, BMS, Immunitas, Legend Biotech, Oncopeptides, and Karyopharm. Consultancy for Genentech and Sanofi. Research funding from Daiichi Sankyo and Regeneron. Krina K. Patel: research funding from Poseida Therapeutics, Cellectis, and AbbVie. Consultancy for Oncopeptides, Nektar, Precision Biosciences, Arcellx, and Bristol Myers Squibb. Consultancy and Research funding from Takeda, Celgene, and Janssen. Gregory Kaufman: funding from BMS and Janssen for the conduct of clinical research. Advisory board/consulting Karyopharm. Elisabet E. Manasanch: consulting fees from Takeda, BMS, Sanofi, GlaxoKlineSmith, and Adaptive Biotechnologies and research funding from Sanofi, Quest Diagnostics, Novartis, JW Pharma, and Merck. Partow Kebriaei: research support from Amgen and Ziopharm. Advisory Board for KITE, Novartis, and Pfizer. Consultancy for Jazz. Sheeba Thomas: research funding from BMS, Ascentage Pharma, X4 Pharma, Acerta, Xencor, and Genentech. Advisory board for Pharmacyclics and Beigene. Member in board of directors for X4 Pharma. Robert Z. Orlowski: Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission. Current equity holder in private company, Patents & Royalties; STATinMED Research: Consultancy; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees. Elizabeth J. Shpall: advisory board to Novartis, Magenta, Adaptimmune, Axio, and Navan. Co-inventor for Takeda. Muzaffar H. Qazilbash: research funding from Janssen, Bioline, Angiocrine, NexImmune, and Amgen. Consultancy to Bioclinica. Advisory board to Bristol-Myers Squib and Oncopeptides.

Data availability statement

The underlying data that support the results in this manuscript are available upon reasonable request to the corresponding author.