Factors associated with unsustained MRD-negativity in patients with MM eligible for transplant

Measurable residual disease (MRD) negativity is increasingly being investigated and used as a biomarker for treatment cessation in patients with multiple myeloma (MM) who are eligible for transplant.

However, MRD resurgence and progressive disease (PD) are observed in some patients posttreatment cessation guided by MRD-negativity; highlighting the importance of identifying  risk factors and predictors of resurgence in this population to prevent disease progression.

Here, we summarize a report published by Guerrero et al.¹ in Blood on the predictors of unsustained MRD-negativity in patients with MM who are eligible for transplant.

Patient population¹

• Individuals enrolled in the GEM2012MENOS65 (NCT01916252) and GEM2014MAIN (NCT02406144) trials who had reached MRD-negativity, as measured by next generation flow were included in this study (N = 267)
• Of these patients, initial MRD-negativity was reached:
  • After induction; 46.8%
  • High-dose therapy/autologous stem cell transplantation; 28.8%
  • Consolidation; 12.0%
  • After 1-year of maintenance; 12.4%
• Median time to initial MRD-negativity was 9 months
• Median follow-up after first MRD-negativity was 73 months
  • Patients were evaluated for MRD resurgence and PD, using next generation flow and stratified by characteristic

Key findings¹

• At follow-up, MRD resurgence or PD was observed in 42% of patients
  • 4% of patients died without PD
• Factors associated with increased MRD-resurgence/PD risk were International Staging System (ISS) score of 3, and ≥0.01% circulating tumor cells (Figure 1).
• Late occurring MRD negativity; defined as MRD-negativity achieved later than post-induction, was also associated with increased resurgence/PD.
• 5-year MRD resurgence and/or PD rates (P < 0.001):
  • 0 risk factors; 16%
  • 1 risk factor; 33%
  • ≥2 risk factors; 57%
• Approximately 15% of patients relapsed without previously observed MRD resurgence
  • 72% of these patients had not received MRD assessment within the last year
• Median PFS from MRD resurgence until either PD or death was 39 months.
• Of patients who relapsed vs those who were progression-free after MRD resurgence, rates of ISS 2 and 3 were significantly higher than ISS 1 at 75% and 46%, respectively (p = 0.03).

CTC, circulating tumor cells; ISS, International Staging System.
*Adapted from Guerrero, et al.¹

Key learnings

Higher circulating tumor cells levels, ISS 3, and later incidence of first MRD-negativity are all predictors of MRD resurgence and/or PD in patients with MM. More frequent MRD assessments are indicated to identify resurgence before patients develop to PD. The identified predictors of resurgence are easily measurable and may aid in the identification of patients who are eligible for treatment cessation onceMRD-negativity is reached.