Predictors of post-transplant measurable residual disease negativity and impact on clinical outcomes in multiple myeloma

Measurable residual disease (MRD) is a powerful prognostic tool in multiple myeloma, but predictors of achieving MRD negativity after autologous stem cell transplantation (ASCT) are not well defined. We studied 814 patients who achieved at least a very good partial response after ASCT between January 2016 and January 2023 and underwent MRD assessment by next-generation flow cytometry (median sensitivity 2.4x10-6). Overall, 48% (n=387) achieved MRD negativity post-ASCT. The presence of t(11;14) (OR 2.1, 95% CI 1.4-3.2; p<0.01) and pre-transplant response less than complete remission (OR 2.1, 95% CI 1.2-3.7; p<0.01) independently predicted MRD positivity. MRD-positive patients had inferior progression-free survival (PFS) (HR 1.99, 95% CI 1.53-2.58; p<0.001) and overall survival (OS) (HR 1.62, 95% CI 1.10-2.28; p=0.009). Despite lower MRD-negative rate, 5-year PFS was similar among t(11;14) MRD-positive (58%) and MRD-negative (63%); p=0.12. The adverse prognostic effect of high-risk cytogenetics (HRCA) on 5-year PFS appears partially mitigated in MRD-negative patients, 5-year PFS was 73% in those without ≥2 HRCA compared with 55% in those with ≥2 HRCA (HR 1.9, 95% CI 1.2-3.3; p=0.01). In the MRD-positive cohort, 5-year PFS was 53% in patients without ≥2 HRCA versus 17% in those with ≥2 HRCA (HR 2.4, 95% CI 1.6-3.6; p<0.01). Additionally, higher residual clonal plasma cell burden within MRD-positive disease was associated with inferior PFS (HR 2.4, 95% CI 1.2-6.9; p=0.002). This study highlights that presence of t(11;14) independently predicts MRD positivity post-ASCT, although it does not significantly impact prognosis in this subgroup.