Key Clinical Summary
- In the phase 3 AURIGA study, daratumumab plus lenalidomide maintenance significantly increased minimal residual disease (MRD)-negative conversion rates compared with lenalidomide alone after autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma.
- Deeper MRD negativity at 10⁻⁶ and sustained MRD negativity for ≥12 months were more frequent with daratumumab-based maintenance.
- Patients achieving deeper or sustained MRD negativity showed trends toward improved progression-free survival.
Minimal residual disease (MRD) status is an increasingly important prognostic marker in multiple myeloma. New data from the phase 3 AURIGA study, presented at ASH 2025, provide detailed insights into MRD dynamics following autologous stem cell transplant (ASCT) in patients receiving daratumumab plus lenalidomide maintenance compared with lenalidomide alone.
Study Design and Results
The AURIGA trial enrolled patients aged 18 to 79 years with newly diagnosed multiple myeloma who achieved at least a very good partial response but remained MRD-positive at a sensitivity of 10⁻⁵ after ASCT. Patients were anti-CD38–naïve and were randomized within 6 months of transplant to receive lenalidomide maintenance alone or in combination with subcutaneous daratumumab for up to 36 cycles.
A total of 200 patients were randomized, with 99 assigned to daratumumab plus lenalidomide and 101 to lenalidomide alone. Baseline characteristics were well balanced between arms. At a median follow-up of 40.3 months, overall MRD-negative conversion rates at 10⁻⁵ were 60.6% in the daratumumab group versus 28.7% with lenalidomide alone (odds ratio [OR], 3.92; P<0.0001). At the deeper threshold of 10⁻⁶, MRD-negative conversion rates were 36.4% and 13.9%, respectively (OR, 3.59; P=0.0003).
At 12 months, nearly half of patients receiving daratumumab-based maintenance achieved MRD negativity at 10⁻⁵, compared with fewer than one in five in the lenalidomide arm. Similar differences were observed at later time points. Sustained MRD negativity lasting at least 12 months was also more common with daratumumab, reaching 29.3% at 10⁻⁵ and 19.2% at 10⁻⁶, compared with 7.9% and 2.0% with lenalidomide alone.
MRD-positive recurrence occurred less frequently among patients achieving deeper MRD negativity and was generally lower in the daratumumab arm. Among patients with sustained MRD negativity at 10⁻⁵, no progression-free survival (PFS) events were observed in the daratumumab group, compared with 25% in the lenalidomide group.
Clinical Implications
These findings reinforce the clinical relevance of both the depth and durability of MRD responses in post-transplant multiple myeloma. Achieving MRD negativity at 10⁻⁶ and maintaining it over time appeared to be associated with fewer MRD recurrences and fewer PFS events, regardless of treatment arm.
For clinicians, the data suggest that adding daratumumab to lenalidomide maintenance can meaningfully increase the likelihood of deep and sustained MRD negativity in anti-CD38–naïve patients after ASCT. The results also support repeated and longitudinal MRD assessments rather than reliance on a single time point, as sustained MRD negativity may better predict long-term disease control.
While trends toward improved PFS were observed, the number of progression events remained low, highlighting the need for continued follow-up to confirm long-term clinical benefit.
Conclusion
At ASH 2025, AURIGA investigators reported that daratumumab plus lenalidomide maintenance deepened and prolonged MRD negativity after ASCT in newly diagnosed multiple myeloma. The findings underscore the value of intensified maintenance strategies and sustained MRD monitoring in optimizing post-transplant outcomes.
Reference
Chung A, Anderson L, Foster L, et al. Minimal residual disease dynamics in post-transplant patients with newly diagnosed multiple myeloma who received daratumumab plus lenalidomide versus lenalidomide alone as maintenance therapy in the auriga study. Presented at: ASH 2025; December 6-9; Orlando, FL.
