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

Anita Kumar, K S Bantilan, A P Jacob, A Park, S F Schoninger, C Sauter, G A Ulaner, C Casulo, M Faham, K A Kong, R K Grewal, J Gerecitano, A Hamilton, P Hamlin, M Matasar, C H Moskowitz, A Noy, M L Palomba, C S Portlock, A Younes, T Willis, A D Zelenetz, Anita Kumar, K S Bantilan, A P Jacob, A Park, S F Schoninger, C Sauter, G A Ulaner, C Casulo, M Faham, K A Kong, R K Grewal, J Gerecitano, A Hamilton, P Hamlin, M Matasar, C H Moskowitz, A Noy, M L Palomba, C S Portlock, A Younes, T Willis, A D Zelenetz

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.

Conflict of interest statement

Disclosure

The authors have stated that they have no conflict of interest.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Clinical Flowchart
Figure 2. Progression-Free Survival
Figure 2. Progression-Free Survival
(A) and Overall Survival (B) and According to Proliferative Index (PI) Higher or Lower Than 30% (C, D) in Intent-to-Treat Population in 23 Patients
Figure 3. MRD Detection Assessed by Adaptive’s…
Figure 3. MRD Detection Assessed by Adaptive’s NGS-MRD Assay. Cell-free (Plasma and Serum) and Cellular (PBMC) Compartments Were Analyzed Separately
Abbreviations: MRD = minimal residual disease; NGS = next-generation sequencing; PBMC = peripheral blood mononuclear cell.

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