Prospective Study of Peripheral Residual Disease (PRD) Monitoring by Clonotypic Mass Spectrometry (EasyM) in Patients with Newly Diagnosed Multiple Myeloma

Study Summary

This prospective, multicenter, investigator-initiated study evaluated EasyM for PRD monitoring in patients with newly diagnosed multiple myeloma (NDMM), including both transplant-eligible and transplant-ineligible patients. The study aimed to compare conventional myeloma assessments and EasyM-based PRD measurements with bone marrow MRD assessed by NGF to determine the potential role of EasyM in clinical practice.

Patient-specific clonotypic peptides were identified at baseline and subsequently tracked using EasyM to monitor changes in serum M-protein levels. Assessments were conducted at baseline, after induction therapy or at month 3 for transplant-ineligible patients, approximately 100 days after autologous stem cell transplantation (ASCT) or at month 6 for transplant-ineligible patients, and every three months thereafter.

A total of 71 patients were pre-screened, of whom 70 met eligibility criteria and had successful baseline clonotypic peptide identification. The study remains ongoing, with a median follow-up of approximately 9.6 months.

Key Findings

Patient characteristics

• 70 eligible patients included in the study

• Median age: 63 years (range 33–83)

• 58% male and 42% female

• 67% transplant-eligible and 22% transplant-ineligible; 5% had yet to start treatment

• 21% of patients with available cytogenetic data had high-risk cytogenetic abnormalities

Disease characteristics

• M-protein subtypes:

  • IgG: 51 patients (74%)

  • IgA: 7 patients (10%)

  • IgD: 1 patient (1.4%)

  • Kappa free light chain: 6 patients (8%)

  • Lambda free light chain: 5 patients (7%)

• Median baseline monoclonal protein concentration was 16.8 g/L among 58 evaluable patients.

• All 70 eligible patients had successful baseline identification of their patient-specific clonotypic peptide, including two patients with M-protein levels below 2 g/L and 11 evaluable patients with light-chain multiple myeloma.

• One screened patient was excluded because free light-chain levels were below the assay’s detection limit.

Sample availability and follow-up

• 92% of patients completed visit 2 assessments.

• 78% completed visit 3 assessments.

• 54% completed visit 4 or later assessments.

• Median follow-up was 9.56 months (range 1–22.6 months).

Comparison with bone marrow MRD

• High positive and negative concordance was observed between EasyM-based PRD assessments and bone marrow MRD measured by NGF.

• Three patients had positive EasyM results despite negative bone marrow MRD. All three had IgG-kappa myeloma.

• The investigators suggested that the longer half-life of IgG antibodies could explain persistent EasyM positivity despite negative bone marrow MRD.

• One of these three patients subsequently became PRD-negative at six months, while follow-up for the other two was ongoing.

Clinical progression and implications

• Two patients experienced rapid clinical progression within one month.

• Two patients showed progression according to EasyM without corresponding progression detected by conventional myeloma testing; additional follow-up was pending.

• These preliminary observations suggest that EasyM may provide complementary information about disease progression between conventional assessments.

• Persistent M-protein detection should be interpreted in the context of immunoglobulin clearance kinetics, particularly for IgG subtypes.

Conclusions

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Authors

Rintu Sharma, Esther Masih-Khan, Harjot Vohra, Sita Bhella, Christine Chen, Vishal Kukreti, Guido Lancman, Keith Stewart, Vathany Kulasingam, Abir Khaled, Zac MacDonald, Bin Ma, Liqiang Yang, Arleigh B. Robertson McCurdy, Suzanne Trudel.