Episode 147: Myeloma Series, Pt. 7 - Transplant Consolidation for Multiple Myeloma (2026)
This week, we discuss the role of the “consolidation” phase of treatment in multiple myeloma, focusing on three key trials: IFM 2009, DETERMINATION, and the MIDAS Trial.
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Autologous stem cell transplant remains our current standard of care for eligible patients for consolidation. Here’s a few important reminders:
VGPR prior to transplant is ideal, but we still transplant those in PR.
For transplant, we want minimum PR with <10% BMPC.
We know there is prognostic significance of VGPR after induction but we don’t know if pushing people from PR to VGPR improves outcomes as opposed to just going to transplant.
What is the historical context of how we got to our current treatment paradigm?
Historically, patients got induction combination cytotoxic chemotherapy with vincristine + doxorubicin + dex (VAD) prior to transplant
Numerous historical studies showed the benefit of high dose melphalan followed by autologous stem cell rescue
Some studies looked at one transplant
Some studies looked at two transplants → AKA “tandem transplant” where patients would get mel + transplant —> recovery (~1-2 month) → another dose of mel + transplant with the idea that this would lead to a deeper, more durable response
As we discussed last week, the doublet and triplet combinations of IMID (thalidomide or revlimid) + dex and PI (velcade) + dex combinations were superior to standard cytotoxic chemotherapy as induction followed by transplant
After that, we progressed to the triplet VRD as standard of care based on SWOG 0777 trial
We then questioned the role of high dose chemotherapy followed by transplant
We thought that patients may achieve deep durable responses with VRD induction mitigating the need for up front high dose melphalan followed by transplant
This led to these two key trials in the modern era
Key Trial #1: IFM 2009 Trial
All patients got RVD induction x 3 cycles
Then randomized to 5 additional cycles of RVD or transplant followed by 2 more cycles of RVD
All received lenalidomide maintenance for 1 year
All patients had stem cells collected regardless of randomization
Primary endpoint: PFS
Included a total of 700 patients
Found PFS benefit but no OS benefit
8 year PFS: 35% vs. 23% → ~10% better PFS
8 year OS: ~60% in both groups
77% in the no up front transplant group got transplant at relapse and had better PFS2 than the early transplant group
Only ~4% of patients got daralutamide or carfilzomib at relapse, evenly distributed between the two groups
MRD was assessed after 1 year of maintenance
Those who were MRD negative had better PFS and OS regardless of which arm the patient had been assigned.
There were more MRD negative patients in the transplant arm which did not translate into OS benefit but did correlate with a PFS benefit.
MRD was done by flow with sensitivity of 10-4 and this was one time point of MRD, not sustained MRD
Key takeaway:
IFM 2009 compared early vs. delayed transplant and showed PFS1 benefit but no OS benefit
35% of patients at 8 year follow up were still in remission → 6 years off treatment (remember only 1 year of maintenance) which is 10% higher than the group who did not get up front transplant
Key trial #2: DETERMINATION Trial
All patients got RVD induction x 1 cycle
Then randomized to 2 additional cycles of RVD followed by transplant or five additional RVD cycles
Both groups received lenalidomide maintenance until disease progression or unacceptable side effects.
Primary endpoint: PFS
Included 873 patients
20% were high risk disease
Median PFS: 67 months (up front transplant) vs. 46 months (no transplant)
This was notably ~20 months longer in both arms compared to IFM 2009 (median PFS 50 months vs. 26 months)
Cross trial comparisons have significant limitations but this suggests that continuous lenalidomide maintenance improves outcomes over 1 year maintenance
No difference in OS despite PFS benefit
With median of over 6 years of follow up, only a little over a quarter (28%) got transplant at relapse in the no transplant arm
Key takeaway: fewer patients got transplant at relapse
Shows the great efficacy of novel agents and really puts into question the need for early transplant for all patients
Those who were MRD negative had better PFS and OS regardless of treatment arm. MRD negative was ~15% higher in the transplant group at the start of maintenance.
What is the argument for early transplant if there is no OS benefit? Why does PFS1 matter?
Each subsequent relapse in MM has shorter PFS likely due to selection of more resistant clones and clonal evolution
Many people believe that there is an “operational cure” (meaning a long, treatment free remission) for patients that can really only be achieved during the first attempt at treatment
Key Trial #3: Midas Trial (published June 2025)
Measurable Residual Disease Therapy in Newly Diagnosed Myeloma
Patients received quadruplet induction therapy with isatuximab, carfilzomib, lenalidomide, and dex (Isa-KRd) for six cycles and were randomly assigned to receive consolidation therapy according to their MRD status.
Patients who were MRD-negative with a sensitivity of 10-5 were assigned to either transplant plus Isa-KRd (2 cycles) or Isa-KRd alone (6 cycles). Patients who were MRD-positive were assigned to either tandem ACT or single ACT plus Isa-KRd (2 cycles).
718 patients
Primary end point: MRD negativity at 10-5 sensitivity before maintenance therapy.
The transplant group did not significantly outperform Isa-KRd alone as consolidation among those who were MRD-negative
Tandem ACT was not superior to single ASCT plus Isa-KRd as consolidation among those who were MRD-positive.
Key takeaway:
Auto-transplant did not improve sustained MRD negativity
Suggests the role of transplant may be different for patients who achieved a deep remission after induction therapy
We have talked a lot about MRD-negativity in this series. How are we integrating this into the current treatment paradigm?
Currently, for those patients who are eligible for transplant, transplant still is the standard of care.
There are trials, such as Master 2 and FASTER , looking at different treatment options and evaluating sustained MRD-negativity, instead of MRD-negativity at a single point in time. Perhaps, there are some patients who may be able to come off of therapy (“treatment free MRD observation”) or even those who can be spared a transplant based on this approach.
These trials are also helping to answer if there is a better way for us to identify who will most benefit from transplant.
At this time, patients with high risk myeloma are recommended to proceed with transplant because maintaining remission has been difficult. What are some of the data in this space?
Some guidelines mention not only a single transplant, but rather a tandem transplant. What is the historical perspective for tandem transplant?
In the mid 90’s the IFM group did a randomized trial looking at single vs. double transplant and found benefit for double transplant particularly for those who did not get to VGPR or better after one transplant
Patients had received Vincristine + doxorubicin + dex induction and interferon maintenance so unclear if tandem transplant is necessary with modern agents
Is a tandem transplant necessary?
STAMINA Trial
Included patients who got 2 to 12 months of induction therapy with mainly RVD but some CyBorD
Randomized 1:1:1
Tandem transplant followed by revlimid maintenance
Singe transplant followed by RVD x 4 consolidation followed by revlimid maintenance
Single transplant followed by revlimid maintenance without consolidation
No improvement in PFS or OS for the more intensive approaches compared to single transplant followed by lenalidomide maintenance
Results contrasted with a European study, the EMN02/HO95 Trial
This study was complicated but it suggested tandem superior and driven mainly by high risk
Several limitations to this study. All patients received CyBorD induction x 4 cycles instead of RVD induction which we know would be inferior especially for high risk patients
If there is no benefit to doing tandem transplant, why is it in the guidelines for high risk?
European study (EMN02/HO95 Trial) did show benefit though hard to draw conclusions with the CyBorD induction approach but technically this result would support tandem approach
In the Midas trial, no benefit was seen with tandem transplant
If you look at those who actually got a second transplant in the STAMINA trial, then there is a significant PFS benefit compared to single transplant for high risk subgroup
Issue is this is a “per protocol analysis” and selecting for patients who likely have better disease biology and performance status introducing a lot of bias
Not appropriately powered to make conclusions
It is only a suggestion to consider tandem but as we have discussed there is no high quality trial level evidence that supports this especially given the intention to treat results in the STAMINA trial
Majority of providers do not routinely perform tandem transplant in high risk and believe the key is maintenance treatment
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The crew behind the magic:
Show outline: Vivek Patel, Sean Taasan, Ronak Mistry
Production and hosts: Sean Taasan, Vivek Patel, Ronak Mistry
Editing: Resonate Recordings
Shownotes: Madeline Fitzpatrick, Ronak Mistry
Graphics, social media management: Ronak Mistry
