Source: Myeloma – Hematology Advisor
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity can safely discontinue maintenance therapy after 2 years, according to research published in Blood.
Researchers found a low risk of disease recurrence at 4 years among patients who discontinued maintenance after receiving it for 2 years and achieving MRD negativity.
This study (ClinicalTrials.gov Identifier: NCT02406144) enrolled 332 patients with newly diagnosed MM who received induction with bortezomib, lenalidomide, and dexamethasone. This was followed by autologous stem cell transplant and consolidation with bortezomib, lenalidomide, and dexamethasone.
Patients were then randomly assigned to receive maintenance with either lenalidomide and dexamethasone (n=161) or ixazomib plus lenalidomide and dexamethasone (n=171). Patients could discontinue maintenance if they had an MRD-negative test result after 24 cycles. Patients who were MRD positive remained on maintenance for 36 more cycles.
At a median follow-up of 69 months, the median progression-free survival (PFS) was not reached in either treatment arm (hazard ratio [HR], 1.136; 95% CI, 0.809-1.603; P =.460). The 6-year PFS rate was 61.3% in the lenalidomide-dexamethasone arm and 55.6% in the ixazomib-lenalidomide-dexamethasone arm.
After 2 years of maintenance, 163 MRD-negative patients stopped treatment, and 63 MRD-positive patients continued on maintenance with lenalidomide and dexamethasone for 3 more years.
Despite the difference in discontinuation, the 4-year PFS rate was significantly higher in the MRD-negative patients than in the MRD-positive patients — 82.8% and 50.4%, respectively (HR, 0.253; 95% CI, 0.149-0.431; P <.0001).
The incidence of grade 3-4 thrombocytopenia was significantly higher in patients who received ixazomib than in those who did not — 16.3% and 7.4%, respectively (P =.011). Grade 3-4 gastrointestinal toxicities were also more common with ixazomib — 15.7% and 2.4%, respectively (P <.0001)
However, there were no significant between-arm differences in grade 3-4 neutropenia, infections, skin toxicities, fatigue, or deep vein thrombosis.
Based on these results, the researchers concluded that lenalidomide and dexamethasone is a “highly effective maintenance regimen” for this patient population.
“Maintenance discontinuation in patients who tested negative for MRD at 2 years resulted in a low progression rate, even in patients with initial high-risk features; however, the impact of treatment discontinuation in patients with undetectable MRD at 2 years should be formally confirmed by prospective randomized studies,” the researchers wrote.
Disclosures: This research was partly supported by Bristol Myers Squibb-Celgene and Takeda. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Rosiñol L, Oriol A, Ríos R, et al. Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma. Blood. Published online November 2, 2023. doi:10.1182/blood.2022019531