Cytogenetic risk stratification combined with minimal residual disease status influences the therapeutic outcome and prognosis of multiple myelomas

Abstract

To explore the value of cytogenetic risk stratification combined with minimal residual disease (MRD) status in predicting the therapeutic efficacy and prognosis for multiple myeloma (MM). From January 2017 to December 2023, 73 cases of newly diagnosed MM were recruited. Cytogenetic risks were stratified according to the results of fluorescence in situ hybridization (FISH); MRD status and clinical data were analyzed. The progression-free survival (PFS) and overall survival (OS), and their influencing factors were evaluated. During the median follow-up period of 30 (4-65) months, the median progression-free survival (PFS) and overall survival (OS) were 38 (95% CI 29.7, 46.3) months and 55 (95% CI 45.9, 64.1) months, respectively. In our cohort, the 3-year PFS rate was 51.0% and the 3-year OS rate was 71.0%. According to the MRD status, 31 MM patients were assigned to the MRD-positivity group and 42 to the MRD-negativity group. Significant differences were detected in the median PFS (30 months vs. 45 months, χ² = 7.747, P = 0.005) and OS (34 months vs. 59 months, χ² = 8.683, P = 0.003) between groups. Subgroup analyses based on the cytogenetic risk stratification (standard risk [SR] and high risk [HR]) showed that MM patients in the SR/MRD-negativity subgroup did not reach the median PFS and OS, and the median PFS (42 months vs. 33 months, P = 0.093) and OS (59 months vs. 42 months, P = 0.703) were similar between the SR/MRD-positivity and HR/MRD-negativity subgroups. In comparison to the HR/MRD-negativity subgroup, the median PFS (20 months vs. 33 months, P = 0.031) and OS (33 months vs. 42 months, P = 0.032) were significantly shorter in the HR/MRD-positivity group. Multivariate analysis showed that MRD-positivity was an independent risk factor for PFS (HR 2.874, 95% CI 1.452, 5.689; P = 0.008) and OS (HR 3.504, 95% CI 1.599, 7.676; P = 0.002) of MM. MRD status is a powerful prognostic indicator of PFS and OS in MM, but its performance is inferior to cytogenetic risk stratification. More high-risk cytogenetic abnormalities (HRCAs) indicate a worse prognosis of MM, while MRD-negativity improves HRCA-associated prognosis of MM. We recommend a risk stratification by assessing MRD status combined with HRCAs in MM patients, thus favoring the design of individualized treatment.

Keywords: FISH; High-risk cytogenetics; Minimal residual disease; Multiple myeloma; Prognostic factor.

Fig. 1

The median PFS (A) and OS (B) in the overall cohort of MM patients.

Fig. 2

The survival of MM patients divided by cytogenetic profiles. A, B The median PFS (A) and OS (B) in MM patients divided by cytogenetic risk stratification. C, D The median PFS (C) and OS (D) in MM patients divided by the number of HRCAs.

Fig. 3

Subgroup analyses on the survival of MM patients. A, B The median PFS (A) and OS (B) in MM patients divided by the MRD status. (C, D) The median PFS (C) and OS (D) in MM patients divided by the cytogenetic risk stratification combined with the MRD status. (E, F) The median PFS (E) and OS (F) in MM patients divided by the clinical response combined with the MRD status.