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KRD vs. VRD as induction before autologous hematopoietic progenitor cell transplantation for high-risk multiple myeloma

Bone Marrow Transplantation volume 57, pages 1142–1149 (2022)Cite this article

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Abstract

Bortezomib, lenalidomide, and dexamethasone (VRD) induction is standard prior to autologous hematopoietic cell transplantation (auto-HCT) in newly diagnosed, high-risk multiple myeloma (ND-HRMM). Carfilzomib (K) is another proteasome inhibitor approved for MM. In this single-center, retrospective analysis, we compared outcomes in ND-HRMM with pre-transplant KRD or VRD induction. High-risk was defined by t(4:14), t(14:16), 1q21 gain/amplification, or del(17p). Primary endpoints were progression-free (PFS) and overall survival (OS). Of 121 ND-HRMM patients, 63 received KRD, and 58 received VRD. Post-induction, complete (CR), very good partial (VGPR), partial response (PR), and overall response (ORR) rates were 23.8%/49.2%/25.4%/98.4% with KRD, and 19%/46.6%/27.6%/93.1% with VRD. At day 100 post-auto-HCT, these were 38.1%/42.9%/19%/100% with KRD, versus 35.1%/49.1%/12.3%/94.8% with VRD. Pre-auto-HCT, 11 (18.3%) KRD and 7 (12.5%) VRD patients had minimal residual disease (MRD)-negative CR (p = 0.45). Post-auto-HCT, 14 (41.2%) and 13 (43.3%) patients had MRD-negative CR (p = 1.000). Median PFS was 38.2 (95%CI 28.7-NA) and 45.9 months (95%CI 43.2-NA) for KRD and VRD, respectively (p = 0.25). Respective 3-year PFS and OS were 53.5% (95%CI 41.1–69.6) and 95.2% (95%CI 90–100) for KRD and 64% (95%CI 51.6–79.5) and 84.2% (95%CI 73.5–96.3, p = 0.30) for VRD. Overall, KRD induction pre-auto-HCT does not improve outcomes. Prospective, randomized studies are needed to confirm these findings.

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Fig. 1: Cumulative incidence of NRM.
Fig. 2: Responses and MRD Evaluation.
Fig. 3: PFS and OS in the KRD and VRD groups.

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Data availability

All the underlying data presented in this study is available upon reasonable request to the corresponding author by email.

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Acknowledgements

EEM and RZO would like to acknowledge support from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and from the Riney Family Multiple Myeloma Research Program.

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Authors and Affiliations

  1. Bone Marrow Transplant and Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA

    Mahmoud R. Gaballa

  2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Junsheng Ma & Roland Bassett

  3. Department of Stem Cell Transplantation & Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Mikael Rauf, Oren Pasvolsky, Mark R. Tanner, Qaiser Bashir, Samer A. Srour, Neeraj Saini, Jeremy Ramdial, Yago Nieto, Regan Murphy, Katayoun Rezvani, Partow Kebriaei, Elizabeth J. Shpall, Richard E. Champlin & Muzaffar H. Qazilbash

  4. Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, Israel

    Oren Pasvolsky

  5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Oren Pasvolsky

  6. Department of Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Guilin Tang & Pei Lin

  7. Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Hans C. Lee, Krina K. Patel, Gregory P. Kaufman, Elisabet E. Manasanch, Sheeba K. Thomas, Donna M. Weber & Robert Z. Orlowski

  8. Ameer-ud-Din Medical College and Lahore General Hospital, Lahore, Pakistan

    Muhammad R. Ullah

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  1. Mahmoud R. Gaballa
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Contributions

MRG and MHQ designed the study, interpreted the data, and wrote the manuscript. JM and RB completed the statistical analysis, interpreted the data, and edited the manuscript. MR, MRT, QB, SAS, NS, JR, YN, RM, KR, GT, PL, HCL, KKP, MRU, GPK, EEM, PK, SKT, DMW, EJS, REC, and RZO provided critical review of the study and edited the manuscript. All authors have approved of the final version of the manuscript.

Corresponding author

Correspondence to Muzaffar H. Qazilbash.

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Ethics approval and patient consent statement

This retrospective chart review 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.

Competing interests

MHQ has research support from Janssen, Angiocrine, NexImmune, and Amgen, and consulting or advisory board with Bioclinica, Bristol–Myers Squib, and Oncopeptides. QB has research support from Stemline, Acrotech, and Takeda, and consulting or advisory board with Takeda, KITE, Amgen, Purdue, and Stemline. YN has research support from Astra Zeneca, Affimed, Novartis, and Secura Bio, and consulting with Affimed. KR has research support from Pharmacyclics and Affimed, personal fees and/or advisory board with Gemoab, AvengeBio, Virogin, GSK, Navan Technologies, and Bayer, and a patent license, royalties, and research agreement from Takeda for work outside of this study. HCL has research support and/or consulting with Daiichi Sankyo, Regeneron, Amgen, Celgene, Janssen, Takeda, GSK, Genentech, Sanofi, BMS, Immunitas Legend Biotech, Oncopeptides, and Karyopharm. KKP has research support and/or consulting from Abbvie, Cellectis, Poseida Therapeutics, Bristol–Myers Squibb, Arcellx, Precision Biosciences, Nektar, Takeda, Celgene, Janssen, and Oncopeptides. GPK has research support from BMS and Janssen, and consulting or advisory board with Karyopharm. EEM has research support from Merck, JW Pharma, Novartis, Quest Diagnostics, and Sanofi, and consulting with Adaptive Biotechnologies, GSK, Sanofi, BMS, and Takeda. PK has research support from Ziopharm and Amgen, and consulting or advisory board with Jazz, Pfizer, Novartis, and KITE. SKT has research support from Genentech, Xencor, Acerta, X4 Pharma, Ascentage Pharma and BMS, and advisory board/board of directors with Beigen, Pharmacyclics, and X4 Pharma. RZO is a founder of Asylia Therapeutics, research support from BioTheryX, CARsgen Therapeutics, Exelixis, Celgene, Janssen, Sanofi, and Takeda, and consulting/advisory board with STATinMED, Sanofi, Servier, Takeda, Amgen, Astra Zeneca, BMS, Celgene, EcoR1 Capital, Genzyme, Forma Therapeutics, GSK, Ionis, Janssen, Juno Therapeutics, KITE, Legend Biotech, Regeneron, and Molecular Partners. EJS is co-inventor for a patent licensed to Takeda and advisory board/consulting with Adaptimmune, Axio, Navan, Novartis, and Magenta. The other authors have not declared a competing interest.

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Gaballa, M.R., Ma, J., Rauf, M. et al. KRD vs. VRD as induction before autologous hematopoietic progenitor cell transplantation for high-risk multiple myeloma. Bone Marrow Transplant 57, 1142–1149 (2022). https://doi.org/10.1038/s41409-022-01697-4

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