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Which Induction Achieves Most MRD-?
Which induction therapy achieves the most MRD negative responses for newly diagnosed myeloma patients? Or I should say which induction therapy leads to the highest percentage of MRD negative patients upon completion of induction therapy only?
I am wondering about standard risk MM patients who may or may not want to have an autologous stem cell transplant (ASCT).
I’ve linked the video below to explain what induction therapy is for newly diagnosed MM patients.
What are the most common myeloma drug regimens for induction therapy?
I am a long-term MM survivor. Standard induction therapy in 1994 when I was diagnosed was VAD aka vincristine, Adriamycin, and dexamethasone. I think that response rates to VAD were about half of what they are with today’s SOC induction therapies.
But this post is taking “overall response rates” to a higher level by isolating not just ORR but the deepest response rate which is MRD negative. I am trying to determine this outcome because many NDMM patients want to
- stabilize their MM while
- undergoing as little toxicity as possible-
MRD negative has shown the longest PFS and OS even without having an ASCT.
Please keep in mind that with increasing response rates, generally, comes increased toxicity. With increased toxicity, generally, comes increased short, long-term and late stage side effects. In my experience oncology does a superficial job of explaining the postential side effects of therapies that you undergo.
Have you been diagnosed with MM? Email me at David.PeopleBeatingCancer@gmail.com to learn more about both conventional and non-conventional MM therapies.
Good luck,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Which chemotherapy induction regimen for newly diagnosed myeloma patients achieves the greatest percentage of MRD negative responses when induction is completed?
Among chemotherapy induction regimens for newly diagnosed multiple myeloma (NDMM), those incorporating anti-CD38 monoclonal antibodies—specifically daratumumab or isatuximab—have demonstrated the highest rates of minimal residual disease (MRD) negativity at the completion of induction therapy.
Top Induction Regimens by MRD Negativity
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Daratumumab + Bortezomib + Lenalidomide + Dexamethasone (D-VRd)
In the phase 3 PERSEUS trial, D-VRd followed by autologous stem cell transplant (ASCT) and consolidation therapy achieved an MRD negativity rate of 57.5% at a sensitivity of 10⁻⁵ at the end of consolidation. This was significantly higher than the 32.5% observed with VRd alone. Additionally, sustained MRD negativity rates over 12 to 36 months were notably higher in the D-VRd arm . -
Isatuximab + Lenalidomide + Bortezomib + Dexamethasone (Isa-RVd)
The GMMG-HD7 trial reported that adding isatuximab to the standard RVd regimen resulted in an MRD negativity rate of 50.1% at the end of induction, compared to 35.6% with RVd alone . -
Isatuximab + Carfilzomib + Lenalidomide + Dexamethasone (Isa-KRd)
In the IsKia trial, the addition of isatuximab to KRd led to an MRD negativity rate of 45% at the end of induction, surpassing the 26% achieved with KRd alone .
Summary Table
| Regimen | MRD Negativity at End of Induction | Sensitivity Level | Trial |
|---|---|---|---|
| D-VRd | 57.5% | 10⁻⁵ | PERSEUS |
| Isa-RVd | 50.1% | 10⁻⁵ | GMMG-HD7 |
| Isa-KRd | 45% | 10⁻⁵ | IsKia |
Minimal Residual Disease Significance in Multiple Myeloma Patients Treated with Anti-CD38 Monoclonal Antibodies
“Abstract
Minimal residual disease (MRD) evaluation is a recognized endpoint in clinical trials. Both next-generation flow and sequencing could be used as complementary techniques to detect myeloma cells after therapy to measure the depth of response and novel drug efficacy.
Anti-CD38 monoclonal antibodies combined with proteasome inhibitors and immunomodulatory drugs have increased the quality of response in myeloma patients, and MRD evaluation is also entering routine clinical practice in many hematological centers.
This review analyzes updated results from recent clinical trials utilizing anti-CD38 monoclonal antibodies such as isatuximab and daratumumab in terms of their responses and MRD data. MRD-driven therapy appears promising for the future of MM patients, and emerging minimally invasive techniques to assess MRD are under investigation as novel potential methods to replace or integrate traditional MRD evaluation…”
which induction achieves the most MRD negative which induction achieves the most MRD negative