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 Journal Article


Authors: Kumar, A.; Bantilan, K. S.; Jacob, A. P.; Park, A.; Schoninger, S. F.; Sauter, C.; Ulaner, G. A.; Casulo, C.; Faham, M.; Kong, K. A.; Grewal, R. K.; Gerecitano, J.; Hamilton, A.; Hamlin, P.; Matasar, M.; Moskowitz, C. H.; Noy, A.; Palomba, M. L.; Portlock, C. S.; Younes, A.; Willis, T.; Zelenetz, A. D.
Article Title: 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
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. © 2020 The Author(s)
Keywords: adult; clinical article; controlled study; aged; human cell; cancer recurrence; cancer combination chemotherapy; cytarabine; rituximab; drug megadose; prospective study; cancer immunotherapy; mantle cell lymphoma; multiple cycle treatment; phase 2 clinical trial; etoposide; melphalan; autologous stem cell transplantation; carmustine; immunoglobulin gene; minimal residual disease; radioimmunotherapy; tositumomab i 131; induction chemotherapy; surveillance; high-dose therapy; high throughput sequencing; human; male; female; article; cyclophosphamide plus doxorubicin plus prednisolone plus rituximab plus vincristine
Journal Title: Clinical Lymphoma, Myeloma and Leukemia
Volume: 21
Issue: 4
ISSN: 2152-2650
Publisher: Elsevier Inc.  
Date Published: 2021-04-01
Start Page: 230
End Page: 237.e12
Language: English
DOI: 10.1016/j.clml.2020.09.007
PUBMED: 33558202
PROVIDER: scopus
PMCID: PMC9476895
DOI/URL:
Notes: Article -- Export Date: 3 May 2021 -- Source: Scopus
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MSK Authors
  1. Gary Ulaner
    146 Ulaner
  2. Carol Portlock
    204 Portlock
  3. Craig Moskowitz
    407 Moskowitz
  4. Ariela Noy
    351 Noy
  5. Maria Lia Palomba
    415 Palomba
  6. Ravinder K Grewal
    82 Grewal
  7. Craig Steven Sauter
    334 Sauter
  8. Andrew D Zelenetz
    767 Zelenetz
  9. Paul Hamlin
    277 Hamlin
  10. Matthew J Matasar
    289 Matasar
  11. Anita Kumar
    180 Kumar
  12. Anna Yong Park
    31 Park
  13. Anas Younes
    319 Younes