Noninvasive Monitoring of Mantle Cell Lymphoma by Immunoglobulin Gene Next-Generation Sequencing in a Phase 2 Study of Sequential Chemoradioimmunotherapy Followed by Autologous Stem-Cell Rescue

Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):230-237.e12. doi: 10.1016/j.clml.2020.09.007. Epub 2021 Jan 1.

Abstract

Background: Minimal residual disease (MRD) monitoring has been used to identify early molecular relapse and predict clinical relapse in mantle cell lymphoma (MCL). Few published data exist in MCL on the performance of next-generation sequencing-based assay of immunoglobulin gene rearrangements for MRD assessment.

Patients and methods: In a prospective clinical trial (NCT01484093) with intensive induction chemotherapy and autologous stem-cell transplantation, posttreatment peripheral blood samples were collected from 16 MCL patients and analyzed with an earlier version of the Adaptive Biotechnologies MRD assay.

Results: Of the 7 patients whose disease remained in remission, the MRD test remained negative in 5 (71%). Of the 9 patients who experienced relapse, the MRD test was positive at least 3 months before relapse in 6 patients (67%) and positive at the time of relapse in 1 patient (11%). All patients with at least 2 positive MRD tests experienced relapse.

Conclusion: The next-generation sequencing-based MRD assay identified early molecular relapse, and we observed more sensitivity in the cellular (circulating leukocytes) versus acellular (plasma cell-free DNA) compartment. This observation may be due to availability of tumor target or a limitation of the assay.

Keywords: High-dose therapy; Minimal residual disease; Surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chemoradiotherapy
  • DNA, Neoplasm / blood*
  • Female
  • Gene Rearrangement
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunoglobulins / genetics
  • Immunotherapy
  • Induction Chemotherapy
  • Lymphoma, Mantle-Cell / blood*
  • Lymphoma, Mantle-Cell / diagnosis*
  • Lymphoma, Mantle-Cell / genetics
  • Lymphoma, Mantle-Cell / therapy
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood*
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm, Residual
  • Neoplastic Cells, Circulating
  • Prospective Studies
  • Remission Induction
  • Stem Cell Transplantation
  • Transplantation, Autologous

Substances

  • DNA, Neoplasm
  • Immunoglobulins

Associated data

  • ClinicalTrials.gov/NCT01484093