Minimal residual disease (MRD) negativity can be sustained for at least one year following the cessation of lenalidomide maintenance in patients with multiple myeloma who have achieved sustained MRD negativity for at least three years, according to data from an observational trial (NCT04221178) presented at the 21st International Myeloma Society Annual Meeting.
Among evaluable patients (n = 39), the MRD-negativity rate at 12 months following the end of maintenance therapy was 85% (95% CI, 64%-94%), including 87% of patients enrolled during stage 1 of the study (n = 15) and 83% of patients enrolled in stage 2 (n = 24).
Neha Korde, MD, lead study author and associate attending physician at Memorial Sloan Kettering Cancer Center, stated that cessation of maintenance therapy is feasible in patients with 3-year sustained MRD negativity. While lenalidomide maintenance improves progression-free survival (PFS) and overall survival in newly diagnosed multiple myeloma patients after autologous stem cell transplant (ASCT), its continuation can negatively impact health-related quality of life (HRQOL) due to adverse effects and financial toxicities.
Study Design and Patient Characteristics
The observational study enrolled patients aged 18 years or older with multiple myeloma who had received any number of prior lines of therapy. Patients were required to have sustained MRD negativity for at least 3 years during continuous maintenance therapy and an ECOG performance status of 2 or less. Patients who were MRD positive at screening, had plasma cell leukemia, received other multiple myeloma treatments (except bisphosphonates), underwent solid organ or allogeneic stem cell transplants, or had conditions requiring immunosuppressive therapy were excluded.
All enrolled patients discontinued maintenance therapy and were monitored for 3 years with serum testing every 3 months, MRD testing via bone marrow every 6 months, and PET-CT scans every 12 months. MRD testing was performed via multiparametric flow cytometry at a 10-5 sensitivity. The primary endpoint was the rate of sustained MRD negativity at 1 year. Secondary endpoints included HRQOL, sustained MRD-negativity rate at 3 years, PFS, event-free survival, duration of MRD response, responses to retreatment, and microbiome and immunosurveillance.
As of the data cutoff date of August 19, 2024, 46 patients had been enrolled with a median follow-up of 24.3 months (95% CI, 20-35). The median time since diagnosis was 8.1 years (range, 5-20), and the median duration of maintenance therapy was 4.6 years (range, 3-13). The mean age was 63 years (range, 29-77), and 67% of patients were male. The majority (77%) had International Staging System (ISS) stage I disease, 21% had stage II, and 7% had stage III.
Prior induction regimens included VRd (bortezomib, lenalidomide, and dexamethasone) in 43% of patients, KRd (carfilzomib, lenalidomide and dexamethasone) in 24%, daratumumab plus KRd in 13%, and other regimens in 20%. Forty-three percent of patients underwent prior ASCT, and all received lenalidomide maintenance.
Efficacy Outcomes
Among patients assessed for MRD after discontinuing maintenance (n = 43), 72% remained MRD negative, and 28% converted to MRD positive. Of those who converted to MRD positive (n = 12), 7 patients did not experience clinical disease progression, while 5 did. The median time to MRD conversion was 16 months (range, 6-49).
At 24 months, the MRD-negativity rate was 78% (95% CI, 66%-93%), and the 24-month treatment-free survival rate was 81% (95% CI, 69%-96%). The 24-month MRD-negativity rate was 81% (95% CI, 68%-98%) for patients with standard-risk cytogenetics and 67% (95% CI, 42%-100%) for those with high-risk or not reported cytogenetics (P = .21).
Patients who received lenalidomide maintenance for more than 1600 days experienced a 24-month MRD-negativity rate of 84% (95% CI, 70%-100%) vs 70% (95% CI, 51%-96%) for those who underwent maintenance for no more than 1600 days (P = .12).
Korde concluded, "In the future, we look forward to ongoing efforts for QOL assessments and immune profiling, including microbiome analysis. We also look forward to further defining phase 3 data from the SWOG 1803/DRAMMATIC trial, which is randomly assigning patients to maintenance continuation vs discontinuation in a 2-year MRD-sustained population."
