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MRD Assessed by Multiparameter Flow Cytometry in Transplant-Eligible Myeloma

By LabMedica International staff writers
Posted on 05 Jul 2021
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Image: The Navios EX flow cytometer offers a solution for advanced cytometry applications with workflows for high throughput laboratories (Photo courtesy of Beckman Coulter)
Image: The Navios EX flow cytometer offers a solution for advanced cytometry applications with workflows for high throughput laboratories (Photo courtesy of Beckman Coulter)
Multiple myeloma (MM) treatment has considerably improved in the past 15–20 years. The current paradigm for transplant-eligible newly diagnosed MM (NDMM) patients consists of induction, stem-cell mobilization and autologous stem-cell transplantation (ASCT), followed by consolidation and/or maintenance.

Currently, minimal residual disease (MRD) assessment is the most sensitive tool to measure the depth of response in MM patients. Indeed, among patients achieving a complete response (CR), MRD-positive patients have an inferior progression-free survival (PFS) and overall survival (OS) compared with MRD-negative ones, and a similar outcome to those achieving a partial response (PR).

A large international team working with Hematologists at the University of Torino (Torino, Italy) conducted an MRD correlative study of a MM phase III trial in newly diagnosed MM patients achieving a suspected complete response before maintenance and every six months during maintenance. Transplant-eligible patients aged ≤65 years were enrolled from February 2011 to April 2014 in 172 European centers. A total of 321 patients before lenalidomide maintenance were evaluated for MRD assessment.

Bone marrow (BM) samples were processed in three European laboratories, applying EuroFlow-based multiparameter flow cytometry (MFC) protocols (eight colors, two tubes) with 10−4−10−5 sensitivity. Data were acquired using a FACSCanto II flow cytometer (BD Biosciences, San Jose, CA, USA). One of the laboratories (Torino) applied a local panel with minor differences in fluorochromes and antibodies; data were acquired using a Navios flow cytometer and analyzed with Kaluza software (Beckman Coulter, Brea, CA, USA).

The clinical scientists reported that at enrollment in the MRD correlative study, 76% (244/321) of patients were MRD-negative. In the intention-to-treat analysis, after a median follow-up of 75 months, 5-year progression-free survival was 66% in MRD-negative versus 31% in MRD-positive patients (Hazard Ratio [HR] = 0.39)), 5-year overall survival was 86% versus 69%, respectively (HR = 0.41). MRD negativity was associated with reduced risk of progression or death in all subgroups, including ISS-III (HR = 0.37) and high-risk fluorescence in situ hybridization (FISH) patients (HR = 0.38).

The authors conclude that their study confirms that MRD status by MFC is a strong prognostic factor in NDMM patients receiving intensification with novel agents or high-dose melphalan (HDM). The achievement of MRD negativity in patients with HR-FISH aberrations was associated with a significantly improved survival, underlining the importance of achieving deep responses in this setting. Finally, lenalidomide maintenance further improved the depth of response in standard-risk patients. The study was published on June 3, 2021 in the journal Blood Cancer Journal.

Related Links:
University of Torino
BD Biosciences
Beckman Coulter

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