Impact of Minimal Residual Disease Status on Multiple Myeloma Outcomes: A Systematic Review
Authors: Amin Muhammad Kashif , Irfan Sohaib , Khan Muhammad Atif , Tuz Zahra Fatima , Mohammad Turab , Mushtaq Muhammad Umair , Shahzad Moazzam 
Published: December 2024

Introduction:
Minimal residual disease (MRD) testing in multiple myeloma (MM) as a potential prognostic and treatment strategy correlates with improved progression-free survival in MRD-negative patients. The use of next-generation sequencing and flow cytometry has allowed for accurate assessment of MRD. This Systematic Review focuses on progression-free survival (PFS) based on MRD status in MM patients, both transplant-eligible and non-eligible. The use of MRD testing can help clinicians predict the efficacy of the treatment regimen and the outcomes for the multiple myeloma patients
Method:
Per PRISMA guidelines, we searched PubMed, clinicaltrial.gov, and Cochrane Library databases using the keywords “Multiple Myeloma OR MM” and “Minimal residual disease OR MRD”. The search strategy yielded 980 studies including clinical trials, abstracts, and cohort studies from the inception till June 30, 2024. Original studies involving adult patients with MM reporting MRD status and outcomes were included. After primary and secondary screening, eight studies were shortlisted for data synthesis. Data were extracted for the total number of patients, age, gender, maintenance therapy, overall survival (OS), and PFS for both MRD-positive (MRD+) and MRD-negative (MRD-) myeloma patients. Descriptive statistics were used, and the results were reported systematically.
Results:
A total of 3640 patients from eight studies were included in this systematic review and meta-analysis. The included were 7 phase III trials (88%) and one phase II trial (12%). The median age of the included patients ranged from 57 to 74 years. 52% of the reported patients were male (1202/2296). Lenalidomide was the most common maintenance therapy reported in 50% of studies. Rawston et al. (2015) reported a median PFS of 1.8 years for MRD+ and 3.1 years for MRD-, while the median OS was 4.4 years in MRD+ and “not reached” in MRD- patients. Tute et al. (2022) reported a median PFS of 44 months for MRD- and 24 months for MRD+, while the median OS was not reached in both groups. Tute et al. (2016) reported a median PFS of 28.6 months for MRD- versus 15.9 months for MRD+, and a median OS of 80.6 months in MRD- compared to 59 months in MRD+. Oliva et al. (2021) reported median PFS of 87 months and 38 months for MRD- and MRD+, respectively with median OS not reached for both. For Paiva et al. (2019), the median PFS was not reached in MRD- and was 36 months in MRD+. The median OS was also not reached for both groups. Loiseau et al. (2017) reported median PFS as 29 months for MRD+ and not reached for MRD- patients. For Tute et al. (2015), the median PFS was 19 and 34 months for MRD+ and MRD-, respectively. Paiva et al. (2023) reported a median PFS of 38.6 months for MRD- patients, and 15.6 months for MRD+ patients.
Discussion:
Minimal residual disease negativity is associated with improved progressive free survival in multiple myeloma patients. The superior progressive free survival highlights the potential of MRD as a promising prognostic factor for survival outcomes and to optimize treatment strategies. More studies exploring the survival outcomes for both MRD+ and MRD- patients will help to understand fully the role of MRD as a prognostic marker.