Minimal residual disease status in multiple myeloma 1 year after autologous hematopoietic cell transplantation and lenalidomide maintenance are associated with long-term overall survival Journal Article


Authors: Pasquini, M. C.; Wallace, P. K.; Logan, B.; Kaur, M.; Tario, J. D. Jr; Howard, A.; Zhang, Y.; Brunstein, C.; Efebera, Y.; Geller, N.; Giralt, S.; Hari, P.; Horowitz, M. M.; Koreth, J.; Krishnan, A.; Landau, H.; Somlo, G.; Shah, N.; Stadtmauer, E.; Vogl, D. T.; Vesole, D. H.; McCarthy, P. L.; Hahn, T.
Article Title: Minimal residual disease status in multiple myeloma 1 year after autologous hematopoietic cell transplantation and lenalidomide maintenance are associated with long-term overall survival
Abstract: PURPOSEPrognostic Immunophenotyping in Myeloma Response (PRIMeR) is an ancillary study of minimal residual disease (MRD) assessment for multiple myeloma by next-generation multiparameter flow cytometry (MFC). Patients were enrolled on a three-arm randomized control trial (Blood and Marrow Transplants Clinical Trials Network 0702 Stem Cell Transplant for Myeloma in Combination of Novel Agents [STaMINA]; ClinicalTrials.gov identifier: NCT01109004).METHODSFour hundred and thirty-five patients consented to the MRD panel, which included 10 monoclonal antibodies measured via six-color MFC. MRD was measured at baseline/preautologous hematopoietic cell transplant (BL/preAutoHCT), premaintenance (PM), and 1 year (Y1) after AutoHCT with a sensitivity of 10-5 to 10-6. The primary objective was to assess MRD-negative (MRDneg) at 1 year after AutoHCT and progression-free survival and overall survival (PFS/OS).RESULTSSimilar to the STaMINA results, at a median follow-up of 70 months, there was no significant difference in PFS/OS by treatment arm in the PRIMeR patients. MRDneg at all three time points was associated with significantly improved PFS, and MRDneg at Y1 had significantly longer OS. Multivariate analysis of PFS, adjusting for disease risk and treatment arm, demonstrated hazard ratios (HRs) in MRD-positive patients compared with MRDneg patients at BL, PM, and Y1 of 1.55 (P =.0074), 1.83 (P =.0007), and 3.61 (P <.0001), respectively. Corresponding HRs for OS were 1.19 (P =.48), 0.88 (P =.68), and 3.36 (P <.001). Patients with sustained MRDneg or who converted to MRDneg by Y1 had similar PFS/OS.CONCLUSIONTo our knowledge, this first, prospective US cooperative group, multicenter study demonstrates that MRDneg at Y1 after AutoHCT with lenalidomide maintenance is prognostic for improved 6-year PFS and OS. Serial MRD measurements may direct trials to test how further therapy may improve long-term PFS and OS. © American Society of Clinical Oncology.
Keywords: adult; cancer survival; controlled study; aged; middle aged; major clinical study; overall survival; lenalidomide; clinical trial; mortality; flow cytometry; follow up; prospective study; progression free survival; bortezomib; multiple myeloma; bone marrow; randomized controlled trial; cytogenetics; dexamethasone; hematopoietic stem cell transplantation; karnofsky performance status; minimal residual disease; neoplasm, residual; multicenter study; immunophenotyping; hazard ratio; transplantation, autologous; therapy; autologous hematopoietic stem cell transplantation; progression-free survival; adverse event; autotransplantation; high throughput sequencing; maintenance chemotherapy; humans; human; male; female; article
Journal Title: Journal of Clinical Oncology
Volume: 42
Issue: 23
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2024-08-10
Start Page: 2757
End Page: 2768
Language: English
DOI: 10.1200/jco.23.00934
PUBMED: 38701390
PROVIDER: scopus
PMCID: PMC11634105
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Sergio Andres Giralt
    1050 Giralt
  2. Heather Jolie Landau
    419 Landau