My approach would be the same for the patient at high risk as it was for the patient with standard risk. My preferred induction treatment is KRd. My next treatment choice would be RVD. If the patient were frail, I would recommend a 2-drug regimen.

I do recognize that a different approach may be necessary for high-risk disease versus standard-risk disease, but I believe we are in need of better defining in a prospective way the best treatment strategy for patients at each risk level. Intuitive selection of more active regimens for only patients with high-risk disease does not appear to be supported by recent data, which show benefit from more active regimens for all risk groups. Modification of our treatment choices could potentially be driven by biomarkers of sensitivity to agents of a given class, such as a certain threshold level of cereblon for lenalidomide, rather than by cytogenetics. I believe that approach has the potential to provide more important information.

My approach will be similar to that used for the patient with standard-risk disease. I would administer RVD for a patient with high-risk disease in the same situation. I believe that patients should receive the best treatment, irrespective of risk.

With a patient at high risk I would favor either VCD or RVD if the patient could tolerate it. RVD lite might be a suitable regimen for older patients with a high cytogenetic risk. If the patient had renal failure I would consider a bortezomib-based regimen because a quick response is needed.

If the patient had high-risk disease, I would consider a bortezomib-based regimen, probably CyBorD continuously until disease progression. I would consider adjusting the dose of bortezomib by reducing it from a once-weekly schedule to every other week. We have learned that patients with high-risk disease should receive a proteasome inhibitor, and for me that is almost always bortezomib.

My treatment recommendation would not change if the patient were at high risk or standard risk. In either scenario, I would administer VMP or lenalidomide in combination with low-dose dexamethasone.

My approach is the same in this situation as it is for a patient at standard risk. For a fit 79-year-old patient with high-risk MM and normal renal function who is transplant ineligible, I would administer either VCD or VMP. If the patient were frail or unfit with comorbidities, I would administer Rd.

My treatment recommendation for a patient with high-risk MM would be the same for one with standard-risk disease. I would administer RVD lite for an otherwise healthy 79-year-old patient with high-risk MM and normal renal function who was ineligible for transplant. Regardless of the risk level, I would administer the best available therapy because we do not have enough data to support recommending the most effective therapy only for patients with high-risk disease.

If the patient had high-risk disease I would recommend RVD lite. With this regimen lenalidomide is administered daily for 21 days of each cycle and bortezomib is administered subcutaneously once weekly. Low-dose dexamethasone is administered on the day of bortezomib administration and the day after.