Evaluation of EuroFlow minimal residual disease measurement and donor chimerism monitoring following tandem auto-allogeneic transplantation for multiple myeloma

Prognostic factors for multiple myeloma (MM) after allogeneic haemopoietic stem cell transplantation (alloHSCT) are poorly characterised. Two potential factors include minimal residual disease (MRD) and CD3 + donor-specific chimerism. We retrospectively examined 93 consecutive patients who received upfront or deferred tandem auto-alloHSCT. Bone marrow (Euroflow) MRD was assessed pre-alloHSCT and 3-monthly post-alloHSCT. CD3 + donor chimerism was assessed at D30, D60, D90, 6 m and 12 m post-alloHSCT. There was no statistical difference between upfront and deferred transplants in progression free survival (PFS) (34 m vs. 15 m respectively, p = 0.20) and overall survival (OS) (75.5 m vs. 62.7 m respectively, p = 0.56). Patients who were MRD-positive post-alloHSCT had inferior PFS to MRD-negative patients from 6 m (6 m HR 3.32, p = 0.02; 9 m HR 4.08, p = 0.003; 12 m HR 4.47, p = 0.008). Attainment or maintenance of MRD-negativity predicted reduced relapse risk (23.5% vs. 62.5%, p = 0.04). However, there was no significant difference in OS between the MRD-negative and positive groups. Full CD3 + donor chimerism at early time points (D30 and D90) was associated with increased risk of acute GVHD (D30 p < 0.001, D90 p = 0.006) and extensive chronic GVHD (D90 p = 0.04), but not PFS or OS. These data support the use of sequential MRD evaluation post-alloHSCT to inform intervention to eradicate persistent or emergent MRD-positive disease.