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

Until recently, my preferred maintenance therapy for patients with standard-risk MM was lenalidomide alone, regardless of whether a patient was in CR or not. I now use 3-drug regimens like CRd or RVD for 4 cycles as consolidation and then move to lenalidomide maintenance.

If a patient achieved a VGPR or PR after transplant, I would also consider consolidation followed by lenalidomide maintenance. I am more consistent about using consolidation post-transplant regardless of the patient’s clinical response based on our study using CRd up front, in which we noted that 100% of patients achieved at least a VGPR after consolidation. I am careful to have a discussion with patients about consolidation because there are limited data and real risks related to myelosuppression, secondary primary malignancy and other toxicities, including more frequent infections. We are trying to balance the benefit of getting a deeper response with these risks, which I feel are all manageable risks. Because we associate a deeper response with improved outcome, I am trying to get my patients to understand that point and why I utilize consolidation treatment.

I would offer this 62-year-old patient who achieved a VGPR or CR after induction therapy and stem cell transplant maintenance therapy with lenalidomide at the 10-mg dose.

If a patient achieved a PR or less, my choice would be to re-treat. This patient has clearly not responded to therapy that included a transplant. However, it also depends on the patient’s disease characteristics. For example, a patient who had an M spike of, say, 5 g/dL prior to treatment and experienced a PR of 50% and the M spike was 2.4 g/dL after treatment has a high disease burden or activity or both versus a patient who had an M spike of 1 g/dL and after treatment had a spike of 0.5 g/dL. Both responses are PRs.

I would probably conduct a bone marrow biopsy on these patients, and I would have a discussion with the patient about additional therapy. I would favor administering more therapy with another triplet or doublet regimen immediately.

Answer: LEN maint if ≥VGPR; RVD lite consol LEN/BTZ maint if PR

We would recommend maintenance therapy with lenalidomide for patients who achieve CR or VGPR. The CALGB-100104 study showed a benefit with lenalidomide maintenance whether or not patients were in complete remission.

For patients who are in PR or less, my approach would be consolidation followed by maintenance. For patients who don’t respond well, I recommend consolidation with a therapy such as RVD lite, for a couple of cycles. I would then switch the patient over to maintenance with lenalidomide and bortezomib.

Until we have more conclusive data, I don’t believe we can recommend that every patient should receive maintenance therapy. Even though maintenance therapy prolongs progression-free survival, there’s still a debate as to whether it prolongs overall survival. We know that it can potentially cause toxicities, including neutropenia and infection. It definitely increases the risk of secondary cancers, in particular myelodysplastic syndromes (MDS). I would want to choose rationally which patients would benefit the most.

I’m more likely to propose maintenance therapy, usually with lenalidomide, for the patient who does not achieve a good response after a transplant. If a patient has a higher burden of disease, I’m concerned that they’re going to experience relapse sooner.

I consider maintenance in all patients, but I tend to push it harder if someone experiences less than a VGPR. It’s a bit of an artificial drawing of the line at VGPR, but it’s the best that we have. I tell patients that with maintenance therapy they are likely to stay in remission longer, but I don't know if it’s going to prolong their life and they will have to remain on continuous therapy.

In France, outside of a protocol we are systematically utilizing 2 cycles of consolidation with a triplet regimen after transplant for all patients if possible.

Data show a survival benefit with lenalidomide maintenance. However, we do not propose maintenance therapy in France, because no drug is approved in this setting. The French guidelines do not recommend maintenance, and the ESMO guidelines do not suggest maintenance either. I believe that in the near future, lenalidomide maintenance will be approved based on data showing that it leads to an overall survival benefit.

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

We don’t have markers that would determine if the disease has been cured. So my preference would be for 2 to 4 cycles of consolidation followed by maintenance irrespective of the patient’s response. Our preference is lenalidomide at 10 mg for 3 weeks on and 1 week off. When we compare consolidation and maintenance in patients in CR versus those in PR, a greater benefit is observed with those in CR.

I would offer maintenance therapy with lenalidomide for standard-risk disease irrespective of the response post-transplant.

Answer: 2-4 cycles RVD consol LEN maint if ≥VGPR 4 cycles RVD consol LEN or LEN /BTZ maint if PR

If a patient achieved a CR after transplant and is otherwise healthy, I would consolidate with 2 cycles of RVD. I would recommend lenalidomide maintenance until disease progression.

For patients who have attained a VGPR, my preference would be consolidation followed by maintenance. The issue would be whether or not the patient achieved a complete remission after consolidation. I would offer them RVD for more than 2 cycles and potentially go for up to 4 cycles of consolidation.

If a patient only achieved a PR, I would definitely consolidate with 4 cycles of RVD and then recommend lenalidomide maintenance. I would consider the characteristics of the disease prior to transplant and determine whether or not the patient would benefit from an augmented maintenance regimen. Augmented maintenance would be lenalidomide 3 weeks on, 1 week off, with bortezomib every 2 weeks.