I generally don’t stratify patients by risk when choosing induction therapy. I treat both standard- and high-risk disease with the same regimen. My preferred induction regimen until recently was RVD (lenalidomide, bortezomib, dexamethasone), but now I more commonly use CRd (carfilzomib, lenalidomide, dexamethasone). That’s emerging as my top choice with the only limitation being whether insurance will approve it or not.

I treat high-risk MM with the same regimen as standard-risk disease. Until recently, my recommendation was RVD. However, now my preferred choice is CRd.

My preference would be a 3-drug combination, RVD, for both standard-risk and high-risk disease. Data suggest that standard-risk disease responds well to these triplet regimens. The Mayo Clinic recommendation would be to administer less intensive therapy to the patient with standard-risk disease and reserve RVD for high-risk disease. But I believe that patients should receive the best treatment, irrespective of risk.

For this scenario, I would recommend RVD. I prefer to be relatively aggressive to control the disease long term because we have good salvage regimens available. I believe that patients should receive the best therapy up front, regardless of their risk status.

I would administer RVD for the patient with high-risk disease in addition to those who are at standard risk. It is particularly important to have a bortezomib-containing regimen for patients who are considered to be at high risk.

I would administer either CyBorD or lenalidomide/dexamethasone. Many people believe that RVD has become standard therapy. But my rationale is that in patients with standard-risk disease, one can treat with an induction regimen that includes either a proteasome inhibitor or an IMiD. I don’t believe we have to treat with both and can save one for later. This is especially true if we’re taking a patient to transplant, which will help us achieve the depth of response that is desired.

For a patient with high-risk disease, I would recommend RVD or CyBorD. We have learned that patients with high-risk disease should receive a proteasome inhibitor, and for me that is almost always bortezomib. I believe it’s rational to administer either CyBorD or RVD, and we have good evidence that both of those are excellent regimens. The advantage of CyBorD is that lenalidomide can be saved for later.

My recommendation would be 4 cycles of VTD (bortezomib, thalidomide and dexamethasone) regardless of the patient’s risk status. That is standard therapy in France and some other countries in Europe and is based on the results of a Phase III study showing that VTD is superior to TD (thalidomide and dexamethasone) for patients with newly diagnosed MM.

I do not modify my strategy according to cytogenetics. I recommend FISH to determine if the patient has t(4;14), t(14;16) or 17p deletion. But a patient with high-risk disease would receive the same treatment. We don’t have any data from Phase III clinical trials addressing the specific issue of the optimal induction regimen. Currently we are initiating a Phase III study comparing VTD to VCD (bortezomib/cyclophosphamide/dexamethasone) as induction therapy in the front-line setting for patients with MM (NCT01971658).

In Italy, there are limitations in terms of what is available and reimbursed. Induction with VTD is available and covered by national insurance. If cost and reimbursement were not an issue, I would recommend bortezomib/cyclophosphamide and dexamethasone for this patient.

I would treat high-risk disease the same as standard-risk disease. Patients who are at low risk can experience remission lasting about 6 to 7 years. Treating high-risk disease with a more aggressive approach might increase the duration of remission from 2 years to about 2.5 years.

I administer RVD because it elicits a high response rate. The goal for a transplant-eligible patient is to reach remission as quickly as possible, with the best effective combination.

The patient’s risk status does not influence my decision. My belief is that you must offer your best treatment up front and take the patient to remission.

RVD would be an excellent choice for this patient. I believe in offering the best treatment to all patients up front. However, if a patient were interested in pursuing a 2-drug regimen, I would consider it reasonable. But that would be the exception rather than the rule.

When I think of high risk, I consider clinical features like extramedullary disease and bone involvement, not just the features that are associated with cytogenetics. However, I don’t necessarily change my choice based on risk. My choice would be RVD irrespective of the risk status. I believe in offering the optimal regimen to all patients because MM is a disease with a uniformly bad prognosis. For a patient with high-risk disease, I would feel even more strongly about offering the patient a proteasome inhibitor as part of their induction regimen.