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. 2023 Nov;12(22):20736-20744.
doi: 10.1002/cam4.6640. Epub 2023 Nov 3.

Minimal residual disease status is the prognostic determinant following high-dose treatment for patients with multiple myeloma

Hareth Nahi  1   2 , Gabriel Afram  2 , Katarina Uttervall  2 , Sandra Lockmer  2 , Love Tätting  1 , Gösta Gahrton  2 , Muhammad Kashif  2 , Evren Alici  2 , Olga Stromberg  3 , Monika Klimkowska  2 , Johan Lund  2
Affiliations

Minimal residual disease status is the prognostic determinant following high-dose treatment for patients with multiple myeloma

Hareth Nahi et al. Cancer Med. 2023 Nov.

Abstract

Background: The presence of minimal residual disease (MRD+) following autologous stem cell transplantation (ASCT) in multiple myeloma represents a poor prognostic factor for progression-free survival (PFS) and overall survival (OS).

Methods: At our department, we recommend lenalidomide maintenance for patients who are MRD+ after ASCT, while MRD-negative (MRD-) patients, after information about the national guidelines, were not advised to follow this regimen.

Results: Out of the total 228 patients, 175 received ASCT following first-line induction (MRD- 92 (53%), MRD+ 83 (47%), at 2 months post-ASCT), while 53 underwent ASCT after second-line treatment (MRD- 27 (51%), MRD+ 26 (49%), at the same time point). Comparatively, MRD- patients who did not receive maintenance demonstrated better OS than MRD+ patients who received upfront ASCT and maintenance treatment (96% vs. 86%, p = 0.030, at 3 years). However, nonsignificant difference was found in PFS (76% vs. 62%, at 3 years). Furthermore, second-line ASCT, MRD- non-maintained patients exhibited significantly better PFS than MRD+ (71% vs. 27%, p > 0.001, at 3 years). However, OS was better but nonsignificant (96% vs. 76%, at 3 years). Fluorescence in situ hybridization (FISH) analysis was performed on 141 out of the 228 patients. Of these, 85 (60%) patients were deemed standard risk (SR), and 56 (40%) were classified as high risk (HR). In the SR cohort, MRD- patients exhibited better PFS and OS than MRD+ patients (71% vs. 59% and 100% vs. 85%, respectively). In the HR cohort, the MRD- patients showed superior PFS but similar OS compared to MRD+ patients (66% vs. 42% and 81% vs. 80%, respectively).

Conclusions: Our results indicate that being MRD- is a more crucial prognostic factor for the 3-year PFS and OS than the presence of high-risk cytogenetic markers or undergoing maintenance treatment. The latter appears insufficient, particularly for MRD+ patients following ASCT in the second-line setting, suggesting that these patients may require a more intensive treatment approach.

Keywords: minimum residual disease; multiple myeloma prognosis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Analysis of progression‐free survival (PFS) in multiple myeloma patients grouped by minimal residual disease (MRD) status. Panel 1A; Kaplan–Meier curves of PFS for all patient grouped by MRD status. Panel 1B; PFS for the first‐line autologous stem cell transplantation (ASCT) patient grouped by MRD status. Panel 1C; PFS for the second‐line ASCT patient grouped by MRD status.
FIGURE 2
FIGURE 2
Analysis of overall survival (OS) in multiple myeloma patients grouped by minimal residual disease (MRD) status. Panel 2A; Kaplan–Meier curves of OS for all patient grouped by MRD status. Panel 2B; OS for the first‐line autologous stem cell transplantation (ASCT) patient grouped by MRD status. Panel 2C; OS for the second‐line ASCT patient grouped by MRD status.
See this image and copyright information in PMC

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