(PA-189) Peripheral Residual Disease (PRD) Monitoring by Clonotypic Mass Spectrometry (EASYM) in patients with Newly Diagnosed Multiple Myeloma

Minimal Residual Disease (MRD) assessment using next generation sequencing (NGS) or next generation flow cytometry (NGF) is a robust predictor of survival outcomes but relies on serial, invasive bone marrow (BM) aspirates, often limited by patchy disease and suboptimal sampling. EASYM (Rapid Novor) is a clonotypic mass spectrometry assay that employs de novo sequencing of the serum M-protein to identify a ‘patient-specific peptide fingerprint” allowing for the quantitative tracking of peripheral residual disease (PRD) (Liyasova 2021).


Methods: This is a prospective, investigator-initiated study in transplant eligible (TE) and transplant ineligible (TIE) newly diagnosed multiple myeloma (NDMM). The study enrols patients within 4 months of treatment initiation; with M protein of
>

2g/L and/or involved free light chains (iFLC) of
>

2000mg/L at screening. Conventional myeloma tests are performed monthly; EASYM is done at screening (visit 1), and q3 months (visit 2+) for TIE patients, or post-induction (visit 2), at day100 post-autologous stem cell transplant (ASCT; visit 3) and q3 monthly (visit 4+) thereafter for TE patients. We aim to prospectively compare conventional myeloma assessments, PRD by EASYM and BM MRD by NGF to establish the role of EASYM in clinical practice.

Results:

As of April 30, 2025, 33 patients had undergone baseline EASYM testing. At screening, the median concentration of M protein was 14.35 (range 2.9-52.9) g/L in 26 patients with measurable intact paraprotein (IgG 67% (n=22) IgA 12% (n=4)) and 2616 (range 22.9-9381) mg/L for the iFLC in 7 light chain myeloma (LC) 21%; kappa=3; lambda=4) patients. All patients (n=32) meeting eligibility criteria had successful baseline identification of a clonotypic peptide, including 6 LC MM. One screen failure was due to iFLC levels lower than detection limit. 28 of 32 patients (85%) were TE. At the time of analysis, 17 (61%) had completed ASCT (15 single, 2 tandem) and 2 had received induction therapy followed by CAR T-cell therapy. Three patients (9%) were TIE, and 1 patient had not yet initiated treatment. At a median follow up of 5 (range 1-13.7) months, 22 and 11 patients had completed the 2^nd and 3^rd visit assessments, respectively. At visit 2, 68% (15/22) had achieved >VGPR, with 9 SPEP(-), 1 SIFE(-) and no PRD(-) by EASYM. At visit 3, 72% (8/11) were in >VGPR with 5 SPEP(-), 3 SIFE(-) and 2 PRD(-) by EASYM highlighting that PRD could still detect M protein in 2 SIFE(-) patients at different time points. At early follow-up, 2 patients had concordant negative PRD and matched marrow MRD (10^-5) by NGF (done within 30 days), 1 patient had both PRD(+) and MRD(+) while 2 MRD(-) patient were still SIFE(+) and PRD(+). To date, no patient has experienced disease progression by conventional assessments or EASYM.


Conclusions:

This ongoing trial explores the potential of EASYM as a sensitive, non-invasive serum-based method for reliably detecting PRD and predicting BM MRD status. Data with longer follow up data will be presented.