(PA-376) Minimal Residual Disease in Newly Diagnosed Multiple Myeloma Patients Not Planned for Upfront Autologous Stem Cell Transplant: Patient Disposition and MRD Outcomes from a Prospective Clinical Trial

Measurable residual disease (MRD) has the potential to guide treatment and promote judicious use of resources in LMICs. However, data on its feasibility and utility in resource-constrained settings remain limited and warrant further study. Here we report patient  disposition, MRD results & characteristics associated with MRD from a prospective study evaluating MRD guided therapy.

Methods:

Newly diagnosed MM patients not intended for ASCT receiving VRd undergo flow-MRD assessment if they achieve at least VGPR post 8 cycles. MRD positive patients are randomised to standard maintenance therapy versus MRD guided consolidation with VRd/KPd till acheivement of MRD negativity for a maximum of additional 12 cycles. 

 

Results:

A total of 279 patients were registered in this clinical trial between July 2022 and June 2024. Of these, 127 (45%) did not undergo MRD evaluation due to the following reasons:: Failure to achieve at least VGPR 50 (17%), deemed unfit for triplet 32 (11%), early mortality 21 (7%), primary refractory disease 12 (4.3%), not keen on for bone marrow 7 (2.5%) and BM MRD not technically feasible in 5 (1.7%).

MRD evaluation was performed in 152 patients after completion of eight cycles. The median age was 55 years (range: 32–79), and 109 (72%) were male. Baseline characteristics include, anemia-86 (56.6%), hypercalcemia 47 (30.9%), lytic bone lesions in 142 (93.4%) and creatinine greater than 2 in 24 (15.8%) patients. The ISS and R-ISS stage distribution is as follows: ISS-I 36(23.7%), ISS-II 44(28.9%) and ISS-III 72 (47.4%) and R- ISS-I 19(12.5%), R-ISS-II 80(52.6%) and R-ISS-III 41(27%). Baseline cytogenetic were: Hyperdiploidy in 73 (48%), t(4:14)- 12 (7.9%), t(14:16)- 7 (4.6%), t(11:14)- 7 (4.6%), del17p in 3 (2%), 1q gain/amp in 44 (29%) and del1p on 3 (2%) patients. IMWG responses at the end of eight cycles shows CR in 96 (64%) and VGPR in 54 (36%).

MRD negativity at a threshold of 10⁻⁵ was achieved in 60 (38.8%) patients, while 92 (60.5%) remained MRD positive. Among these groups, MRD positivity was significantly higher among patients in VGPR compared to those in CR (52% vs 10%, p < 0.001). However, other baseline characteristics, including ISS stage and cytogenetics, were not statistically different.

At a median follow-up of 21.8 months, the median PFS and OS of the cohort have not yet been reached. Of the 22 progression events, 17 (18.5%) occurred in the MRD-positive cohort and 5 (8.5%) in the MRD-negative cohort (p = 0.041). A total of 6 deaths occurred (all due to disease progression): 4 in the MRD-positive and 2 in the MRD-negative cohort (p = NS).

Conclusions:

MRD assessment is feasible and prognostically relevant in our setting. MRD negativity was less frequent among patients achieving VGPR, while other baseline prognostic markers showed no significant association with MRD status. A substantial proportion of patients did not undergo MRD testing after eight cycles due to suboptimal response, highlighting the need for more effective frontline therapies.