Implementation and utility of measurable residual disease (MRD) testing for multiple myeloma patients at a VA medical center Free

Measurable residual disease (MRD) testing in myeloma has been shown to be a strong prognostic marker for progression-free and overall survival. It may also be useful for making therapeutic decisions. The clonoSEQ Assay utilizes next generation sequencing involving a bone marrow sample, obtained at the time of diagnosis, to identify patient-specific sequence(s). The same methodology is then applied later to assess for MRD. Although widely adopted at most US academic centers, until recently there has been very limited use of MRD across VA centers. In an effort to improve this gap in quality of care, in 2022 the Cleveland Louis Stokes VA Medical Center partnered with Adaptive Biotechnologies to develop a process for MRD/clonoSEQ testing in myeloma pts. Hematology, Pathology, Medicine, Administration and Adaptive Biotechnologies representatives met to develop a streamlined process for ordering, sample procurement, billing and result documentation. In 5/2022 the 1^st specimen was sent; in 2023 we showed that it was cost effective for the institution¹ and extended testing for MRD on all myeloma pts w/VGPR or better, both transplant- eligible and ineligible. We now present the results of this quality improvement in terms of feasibility for implementing MRD testing and its use in management decisions for veterans at our institution.

Methods:

All myeloma pts had initial marrow specimens sent for ClonoSeq ID testing; those who had a VGPR or better at Cleveland VAMC from 5/2022-6/2025 had MRD tracking sent. Turnaround time, demographics and effect of MRD results on treatment decisions were documented. MRD-negative was defined as less than 5 in 1x10⁶ cells. Pts who did not have an identifiable sequence ID or inadequate marrow on follow-up went on to have peripheral blood mass spectrometry sent.

Results:

49 veterans had samples sent for sequence identification, and 32 subsequently had samples sent for MRD tracking, including 2 for mass spec. Med age was 72.5 (46-82); 94% male; 59% white, 41% black; 12/32 (37.5%) had prior Agent Orange exposure. The median turnaround time from bone marrow sample collection to result report was 8 days (range 4-15 days); 48/49 had a sequence identified for MRD tracking. Of the 32 MRD tracking specimens, 15 (47%) were sent post-autologous stem cell transplant (SCT) and 17 (53%) were sent in the SCT ineligible setting. Of the post-SCT specimens, 6/15 (40%) were MRD negative; 8/17 (47%) in non-SCT setting were MRD negative, with 2 additional pts negative on mass spec. Overall, 15/32 (47%) patients had therapy discontinued based on MRD or mass spec negativity; 6 of these 15 had minor side effects (all associated with lenalidomide) in addition to MRD negativity which led to treatment discontinuation. The median duration of the treatment before it was stopped was 2.65 years (range 0.2-14.5 years). Of those who stopped treatment: 5 were post-SCT; 9 SCT-ineligible during maintenance following induction, and 1 during treatment of relapse. High risk FISH findings in those stopping treatment: 2 pts post-SCTx (gain 1q, and other had del 17p) and 4 SCT-ineligible (3 pts with gain 1q, 1 with del 17p); none had >1 high risk FISH. The median follow-up time after stopping treatment based on MRD was 6 months (range 2-19 months) and none have yet experienced disease recurrence.

Conclusions:

MRD testing for veterans with myeloma was shown to be feasible, efficient and results often (47% of time) contributed to decisions for treatment discontinuation. Longer follow-up is needed to determine outcomes in those who had therapy stopped based on MRD results.

¹O'Brien T, Augustine S and Ansari M. Clonoseq testing for minimal residual disease in multiple myeloma: Cleveland VA experience and cost analysis. AVAHO abstract, Sept 2023.