MRD Status at Serial ASCT Time Point Are Positive Predictors for Survival Outcomes in Multiple Myeloma

Minimal residual disease (MRD) status 3 months after autologous stem-cell transplant and before maintenance assignment (ASCT +3) and 6 months after ASCT (ASCT +9) were robust predictors for progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma, according to a study published in The Journal of Clinical Oncology.

Of 750 patients, 475 at ASCT +3 were MRD-negative and 275 MRD-positive. Those who were MRD-negative had a significantly improved PFS of 44 months vs 24 months for those who were MRD-positive (HR, 0.47; 95% CI, 0.37-0.58; P <.0001). Moreover, the 3-year OS rate increased from 78.7% (95% CI, 72.9% to 84.4%) of MRD-positive patients to 86.5% of MRD-negative patients (95% CI, 82.2% to 90.7%; HR, 0.59; 95% CI, 0.40-0.85; P = .0046). Of those with ASCT +9 were 214 patients who were MRD-negative and 112 who were MRD-positive. MRD-negative had improved PFS by 50 months vs 13 months in those who were MRD-positive; the difference between groups appeared to be statistically significant (HR, 0.59; 95% CI, 0.40-0.85; P <.0001).

In the trial, transplant-eligible patients were randomly assigned to either the lenalidomide group (n = 730) or the observation group (n = 518) 3 months after receiving ASCT. Of the overall population, 818 patients had ASCT +3 bone samples sent for testing, 750 of which were informative of MRD status.

The median follow-up was 32.9 months. Patients who were MRD-negative at ASCT +3, treatment with lenalidomide was associated with an improved median PFS from 36.0 months to 56.0 months (HR, 0.63; 95% CI, 0.45-0.86; P <.0042). For those who were MRD-positive at ASCT +3, treatment with lenalidomide was associated with an improved in median PFS from 18 months with observation to 33 months with lenalidomide (HR, 0.43; 95% CI, 0.32-0.60; P <.0001). Additionally, lenalidomide was associated with an improvement in 3-year OS rate from 83.4% with observation to 88.9% with lenalidomide for those who were MRD-negative at ASCT +3. There was also an association for those who were MRD-positive at ASCT +3, with an improvement in OS rate at 3 years from 75.4% with observation to 81.4% with lenalidomide.

The OS had increased at 3 years from 69.5% (95% CI, 55.0%-84.0%) in MRD-positive patients to 86.9% (95% CI, 78.0-95.7%) in patients who were MRD negative at ASCT +9; the difference between groups significantly favored the MRD-negative arm (HR, 0.33; 95% CI, 0.15-0.75; P = .0077). Regardless of MRD status, at ASCT +3 and +9, lenalidomide maintenance therapy was associated with significant PFS benefit vs observation. In those who were MRD negative at ASCT +9, lenalidomide was associated with improved PFS, with a median of 31 months with observation to not yet having been observed with lenalidomide (HR, 0.32; 95% CI, 0.15-0.67; P = .0025). Lenalidomide was also associated with an improved PFS for those with MRD-positivity at ASCT +9 with a median of 9 months for the observation group and 47 months with lenalidomide (HR, 0.41; 95% CI, 0.25-0.69; P = .0008). There was also an association for those who were MRD-negative at ASCT +9 with improved 3-year OS rate of 58.0% for the observation group to 83.1% in the lenalidomide group.

A logistic regression analysis determined that the MRD status at ASCT +3 for patients receiving lenalidomide had 47% higher odd being MRD-negative at ASCT +9, but did not reach statistical significance (OR, 1.47; 95% CI, 0.70-3.09; P = .3035).

At 3 years, those with sustained MRD negativity had a PFS rate of 63.5% and an OS of 81.5%. Nineteen of 75 patients converted from MRD positivity at ASCT +3 to MRD negativity at ASCT +9. This occurred in the induction therapy subgroup, and both the standard- and high-risk subgroups. Fourteen of 46 patients who were MRD positive at ASCT +3 and received lenalidomide maintenance achieved MRD negativity at ASCT +9. Additionally, 22 of 170 patients converted from MRD-negative at ASCT +3 to MRD-positive at ASCT +9.

Shorted PFS was observed in MRD-negative patients who had one or more high-risk lesions vs MRD-negative standard-risk lesions (33 months vs 63 months; HR, 2.57; 95% CI, 1.55-4.26; P = .0002). Investigators noted that this meant patients who achieved high MRD negativity could not overcome adverse PFS associated with genetic high-risk factors. A shorted OS was observed in MRD-negative patients who were high and/or ultra-high-risk vs MRD-negative standard-risk patients; the median OS was not reached compared with 45.0 months, respectively (HR, 3.25; 95% CI, 1.37-7.75; P = .0078).

Reference

de Tute RM, Pawlyn C, Cairns DA, et al. Minimal residual disease after autologous stem-cell transplant for patients with myeloma: prognostic significance and the impact of lenalidomide maintenance and molecular risk. J Clin Oncol. Published Online April 4, 2022. doi:10.1200/JCO.21.02228