Answer: 4 cycles CRd or RVD consol LEN maint, regardless of post-ASCT response

Data from Nooka and colleagues suggest that 3-drug combinations like RVD for consolidation and maintenance provide excellent outcomes for patients with high-risk MM. If I use CRd for induction, I would continue that combination as post-transplant consolidation. For a patient who had received RVD prior to transplant, I would suggest RVD post-transplant.

I associate deepened responses with improved progression-free survival, so if a patient has some residual disease that is sensitive to treatment, why not use consolidation to attempt to further eliminate the disease. I want to provide this opportunity to my patient.

I generally recommend 4 cycles of consolidation with CRd or RVD and then single-agent lenalidomide maintenance regardless of status of the disease. But I believe that RVD or CRd treatment beyond 4 cycles in high-risk disease would be reasonable.

We do not have randomized data showing that a particular regimen is superior. Both RVD and lenalidomide are good options for a patient with a CR or VGPR. I’ve administered treatment to patients with CRd without transplant for 8 cycles and put them on lenalidomide. Of the many high-risk cases I’ve treated, only one progressed almost 3 years later. So I believe that with good induction therapy you can administer less intense maintenance. But if you have inferior combination therapy followed by transplant, more therapy may be needed later.

If the patient achieved a PR or less, I would recommend re-treating. My choice would be VTD-PACE.

Answer: RVD lite consol LEN maint if ≥VGPR, RVD lite consol RVD lite maint if PR

For patients with high-risk disease who have achieved a VGPR or CR, I would consider consolidation followed by maintenance. Data from the IFM 2005-02 study suggest that patients with high-risk cytogenetic features benefited from lenalidomide maintenance. My preference would be consolidation with RVD lite, using lenalidomide and bortezomib with steroids to control the disease. I do believe that patients with high-risk disease will experience disease progression. After consolidation I would recommend maintenance with lenalidomide.

If a patient with high-risk features had a PR after transplant, I would consider RVD lite and then maintenance with lenalidomide and bortezomib with dexamethasone, preferably in lower doses so that it would be tolerable for the patient.

Answer: Consol  BTZ maint if CR; Consol BTZ-based maint if ≥VGPR

Patients with high-risk disease are more likely to experience early relapse. Emerging evidence suggests that with the high rate of relapse, continuous therapy would be beneficial in these patients. So I firmly believe that maintenance therapy should be offered to these patients. I recommend maintenance with bortezomib for patients who are in CR post-transplant.

The depth of response is important in high-risk disease. I would recommend consolidation for patients who have only achieved a VGPR or PR prior to maintenance. So, whereas I’m okay with starting a patient with standard-risk disease on maintenance with lenalidomide, I want to take patients with high-risk disease to complete remission with more aggressive therapy and then follow with more gentle maintenance therapy containing bortezomib.

In France, no agent has been approved for maintenance therapy, so I do not recommend it off protocol. We do recommend 2 cycles of consolidation for all patients after transplant.

Answer: 2-4 cycles consol LEN maint regardless of post-ASCT response

My recommendation is consolidation and maintenance for these patients irrespective of the level of response. I would offer patients 2 to 4 cycles of consolidation followed by maintenance lenalidomide at the 10-mg dose, 3 weeks on and 1 week off.

Answer: Possibly RVD consol LEN/BTZ maint regardless of post-ASCT response

For patients who have high-risk features like deletion 17p or t(14;16), I would consider lenalidomide and bortezomib regardless of the level of response. For patients with high-risk cytogenetic features, I may also consider administering a few cycles of RVD consolidation after transplant, especially if I am concerned that the patient had an insufficient level of exposure to a proteasome inhibitor as induction prior to transplant. I don’t worry to the same extent in the case of the immunomodulatory agent (IMiD) because I will use the IMiD as part of maintenance therapy regardless.

Answer: 4 cycles RVD consol LEN/BTZ maint regardless of post-ASCT response

My recommendation would be for 4 cycles of RVD consolidation followed by maintenance with a combination of lenalidomide and bortezomib for patients with high-risk disease who had achieved a CR, VGPR or PR.