P-085: The Use of Clonotypic Mass Spectrometry for Post-AHCT Blood-Based Measurable Residual Disease Monitoring in Patients with Light Chain Multiple Myeloma

Introduction: Given the invasive nature of bone marrow sampling, there is growing interest in blood-based methods of measurable residual disease (MRD) testing for patients with multiple myeloma (MM). We previously reported data utilizing clonotypic mass spectrometry (MS) in patients with intact immunoglobulin M-protein (Slade, ASH 2022). However, 10-20% of patients present with light chain (LC) M-protein and data on the feasibility of clonotypic MS in these patients is limited.

Methods: Given the invasive nature of bone marrow sampling, there is growing interest in blood-based methods of measurable residual disease (MRD) testing for patients with multiple myeloma (MM). We previously reported data utilizing clonotypic mass spectrometry (MS) in patients with intact immunoglobulin M-protein (Slade, ASH 2022). However, 10-20% of patients present with light chain (LC) M-protein and data on the feasibility of clonotypic MS in these patients is limited.

Results: Of 17 patients analyzed, 15 had a measurable clonotypic signature at diagnosis while 2 did not and were excluded from further analysis. Fourteen patients were White and 8 were male. Three, 8 and 4 patients were R-ISS stage I, II and III. The median age at AHCT was 59 (range: 45 – 76). The median difference in FLC (dFLC) at diagnosis was 265 mg/dL (range: 43 – 1449) and median EasyM was 5.62 arbitrary units (AU) (range 0.16 – 207.86). The lower limit of quantification varied given the unique clonotypic signature of each M-protein, with a median of 0.0088 AU (range: 0.00094 – 0.033) and median % quantifiable reduction in EasyM of 99.87% (range: 95.86 – 99.99%).

At day +100, 14 patients (93%) were in CR. One was in VGPR at day +100. The median dFLC was 0.10 mg/dL (range 0.00 – 0.99). 8 (53%) had no detectable disease by EasyM (MRD-) at day +100; 7 (47%) had residual disease (MRD+). The median % residual EasyM in MRD+ patients was 0.20% of baseline (range 0.02 – 1.12%). Median baseline dFLC (249 vs. 270 mg/dL) and EasyM (0.78 vs. 10.32 AU) were numerically lower in the MRD- group, though these differences did not reach statistical significance.

Median follow up was 4.4 years. At last follow up, 4 of 7 patients in the MRD+ group had relapsed and 3 had died. One MRD- patient died in remission from infection on day +619. The remainder of the MRD- patients remain alive and disease-free at a median of 3.9 years (range: 1.0 – 8.3) post-AHCT.

Conclusions: In this study, we showed that EasyM generates a trackable clonotype in the vast majority (88%) of patients with LC MM and that relapse was numerically higher in patients with normal dFLC and MRD+ by EasyM at day +100 after AHCT. Defining the clinical application of EasyM requires larger studies with additional time-points, but this series demonstrated that it may be a useful tool for disease monitoring in LC MM.