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

Article

Minimal residual disease status 3 months and 6 months following autologous stem-cell transplant could be predictive of progression-free survival and overall 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

Related Videos
A panel of 4 experts on multiple myeloma
A panel of 4 experts on multiple myeloma
A panel of 4 experts on multiple myeloma
A panel of 4 experts on multiple myeloma
A panel of 4 experts on multiple myeloma
A panel of 4 experts on multiple myeloma
Samer A. Al'Hadidi, MD, with Rahul Gosain, MD, and Rohit Gosain, MD
Samer A. Al'Hadidi, MD, with Rahul Gosain, MD, and Rohit Gosain, MD
Samer A. Al'Hadidi, MD, with Rahul Gosain, MD, and Rohit Gosain, MD
Samer A. Al'Hadidi, MD, with Rahul Gosain, MD, and Rohit Gosain, MD
Related Content