Impact of Post-Transplant Response and Minimal Residual Disease on Survival in Myeloma with High-Risk Cytogenetics

- In high-risk (HR) patients by FISH, post-ASCT sCR leads to superior PFS but not OS.
- Post-ASCT MRD negativity leads to a superior PFS and OS.
- sCR and MRD status did not impact PFS or OS in del(17p) and ≥2 HR subgroups.
- In the subgroup with t(4;14), post-ASCT MRD negativity improved PFS and OS.

The impact of depth of response and minimal residual disease (MRD) status on survival is not well defined in multiple myeloma (MM) with high-risk (HR) cytogenetics because of the low representation of such patients in clinical trials. We have evaluated the impact of post-transplant stringent complete response (sCR) and MRD status on progression-free survival (PFS) and overall survival (OS) in 185 consecutive MM patients with HR fluorescence in situ hybridization cytogenetics undergoing upfront autologous stem cell transplantation between 2007 and 2015 in our institution. The median age at transplant was 61 years. Post-transplant sCR was achieved by 42 patients (23%). Patients achieving sCR had a superior PFS (median, 38 versus 21 months) compared with those who did not (P = .002). One hundred three patients (56%) were MRD negative on day 100 by 6- or 7-color flow cytometry. Patients achieving MRD negativity had a superior PFS (median, 26 versus 17 months; P < .001) and superior OS (5-year OS rate, 64% versus 41%; P = .023) compared with MRD-positive patients. In the subgroups with deletion(17p) (n = 84) and those with ≥2 HR cytogenetic abnormalities (n = 32), sCR and MRD negativity did not translate into a superior PFS or OS. In patients with t(4;14) (n = 65), sCR post-transplant led to a trend toward superior PFS and MRD negativity translated into significantly superior PFS and OS. Depth of response and MRD status are important surrogate markers for survival in patients with HR cytogenetics, except in the subgroups with deletion(17p) and ≥2 HR abnormalities, where sCR and MRD negativity post-transplant did not translate into a superior survival.