MRD Testing in Newly Diagnosed Myeloma Patients: A Path to Better Outcomes

Minimal residual disease (MRD) refers to the small number of cancer cells that may remain in the body after treatment, even when a patient appears to be in remission. In multiple myeloma, achieving MRD negativity—where no detectable cancer cells remain—has become a key indicator of how well a treatment is working and is strongly linked to longer progression-free survival (PFS).

While achieving MRD negativity is associated with better outcomes, it's important to understand that many patients live long, quality lives while being MRD positive but with well-controlled disease. MRD testing provides valuable information about your disease status, and tracking MRD trends over time can often be more informative than focusing solely on negative or positive results. 

Recent studies presented at the 2024 American Society of Hematology (ASH) conference highlight how MRD status can significantly impact outcomes for newly diagnosed multiple myeloma (NDMM) patients, regardless of whether they are eligible for a stem cell transplant.

Transplant-Eligible Patients: How Adding Isatuximab Improves Outcomes

The following information comes from the ASH Abstract, Impact of Minimal Residual Disease on Progression-Free Survival in Patients with Newly Diagnosed Multiple Myeloma Treated with Isatuximab, Lenalidomide, Bortezomib and Dexamethasone Induction Therapy in the Phase 3 GMMG-HD7 Trial. 

The Phase 3 GMMG-HD7 trial investigated the impact of adding the anti-CD38 monoclonal antibody isatuximab (Isa; Sarclisa, Sanofi) to the standard treatment regimen of lenalidomide, bortezomib, and dexamethasone (RVd) in transplant-eligible NDMM patients. Results showed that Isa-RVd led to significantly higher MRD negativity rates after induction therapy compared to RVd alone (50% vs. 36%).

Key findings include:

• Patients who achieved MRD negativity had a 3-year PFS rate of 88%, compared to 71% in patients who remained MRD-positive.
• Patients who maintained MRD negativity after induction and stem cell transplant had even better outcomes, with a 90% 3-year PFS compared to 77% in those without sustained MRD negativity.
• Even patients who did not achieve MRD negativity benefited from the addition of Isa, showing longer progression-free survival (time without disease progression) than those who received RVd alone.

These results emphasize that achieving and maintaining MRD negativity is a strong predictor of better long-term outcomes for transplant-eligible patients.

Transplant-Ineligible Patients: Daratumumab's Impact on Treatment Success

The next section highlights information from the ASH abstract, Expanded Analysis of MRD Outcomes from the Phase 3 CEPHEUS Study on Daratumumab with VRd in Transplant-Ineligible Newly Diagnosed Multiple Myeloma. 

The Phase 3 CEPHEUS study explored the addition of daratumumab (Darazalex Faspro, Johnson & Johnson) to VRd therapy (bortezomib, lenalidomide, and dexamethasone) in newly diagnosed multiple myeloma patients who were ineligible for transplant or had deferred transplant.

Key findings include:

• MRD negativity rates were significantly higher with D-VRd compared to VRd alone: 61% vs. 39% at the 10⁻⁵ sensitivity level (that is, the capacity to detect 1 cancer cell amongst 100,000 cells).
• Sustained MRD negativity for ≥12 months was also higher with D-VRd: 49% vs. 26%.
• These deeper responses translated into better outcomes: patients in the D-VRd group had a 54-month PFS rate of 81% for MRD-negative patients compared to 70% for VRd alone.

This data shows that even for patients who are not candidates for a transplant, achieving MRD negativity can significantly improve long-term survival outcomes.

What MRD Testing Means for Newly Diagnosed Myeloma Patients

Whether or not you are eligible for a stem cell transplant, these studies provide reassuring evidence that achieving MRD negativity is closely linked to better outcomes in multiple myeloma. The addition of monoclonal antibodies like isatuximab and daratumumab to standard treatment regimens can help more patients reach this important milestone.

Key Takeaways:

• MRD negativity is a powerful predictor of longer progression-free survival.
• Monoclonal antibodies (isatuximab and daratumumab) combined with standard therapies improve the chances of achieving MRD negativity.
• Sustained MRD negativity leads to even better long-term outcomes.
• These findings apply to both transplant-eligible and transplant-ineligible patients.

For newly diagnosed patients, these results highlight the importance of discussing MRD testing and treatment options with your healthcare team to better understand how your treatment plan can be optimized for the best possible outcomes.

Want to understand how MRD testing affects your myeloma treatment journey? Our comprehensive MRD Patient Guide explains when and how MRD is measured, what your results mean, and how this information can help guide your treatment decisions. Knowledge is power—explore the HealthTree MRD Patient Guide today to become a more informed advocate for your care.

MRD GUIDE

Sources: 

• Phase 3 Randomized Study of Daratumumab (DARA) + Bortezomib, Lenalidomide and Dexamethasone (VRd) Versus Alone in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma or for Whom Transplant Is Not Planned As Initial Therapy: Analysis of Minimal Residual Disease in the Cepheus Trial
• Impact of Minimal Residual Disease on Progression-Free Survival in Patients with Newly Diagnosed Multiple Myeloma Treated with Isatuximab, Lenalidomide, Bortezomib and Dexamethasone Induction Therapy in the Phase 3 GMMG-HD7 Trial