I continue induction therapy for patients until disease progression. With both the KRd and RVD regimens, patients need to be regularly assessed and feedback from nurses should be obtained. Patients should be made aware of toxicities and how to manage them.

Dose modification is needed for a majority of patients during the extended KRd treatment. To limit toxicities I reduce the dose of dexamethasone after 4 cycles from 40 mg to 20 mg weekly. The schedule of carfilzomib is also altered from 2 consecutive days each week for 3 weeks of a 4-week cycle to 2 consecutive days every other week.

With RVD I generally recommend more intensive therapy for the first 4 cycles. I reduce the dose of dexamethasone from cycle 5 and administer lenalidomide for 21 days. With bortezomib, depending on the emergence of toxicities, between cycles 4 and 8 I switch to a weekly schedule. It is important to monitor the emergence of peripheral neuropathy with bortezomib because that will affect the ability to administer the drug long term.

With both KRd and RVD I would consider converting treatment to single-agent lenalidomide, based on toxicities.

Answer: Treat until CR or 2 cycles after response plateau LEN maint. until PD

I would probably recommend induction therapy for a total of 9 to 12 months while continually monitoring the response. If the patient has a good response and the toxicities are acceptable, I would continue therapy. I would administer treatment for 2 cycles or so beyond the response plateau and then switch to lenalidomide maintenance. If the patient achieved complete CR during induction therapy, I would immediately administer maintenance lenalidomide.

I would use the same maintenance lenalidomide dose for an older patient as I would for one who is younger. However, I will monitor the older patient and ensure that the therapy is well tolerated. I may have to reduce the dose of lenalidomide from 10 mg daily to 5 mg every other day for the elderly patient, depending on tolerability.

For a patient who is at standard risk, continuing induction therapy until disease progression is reasonable if it is tolerated, in keeping with the results of the Phase III FIRST (MM-020/IFM 07 01) trial. That was an interesting study because in terms of progression-free survival, Rd for 18 cycles was inferior to the same regimen administered until disease progression. The benefit in terms of overall survival is still not clear. If tolerability becomes an issue, I’ll dose reduce in order not to negatively impact the patient’s quality of life.

Patients who are on a bortezomib regimen should be continually monitored and asked if they are experiencing peripheral neuropathy because it is important to address that early.

I would recommend treatment until disease progression because of what we learned from the Phase III FIRST trial. Patients who stopped therapy after 18 months did not have as good an outcome as those who stayed on it indefinitely.

For most patients lenalidomide may cause fatigue or lower blood counts. Generally I make my treatment decision at the initiation of therapy. For the majority of 80-year-old patients I would initiate lenalidomide at a lower dose of 10 to 15 mg once daily. Age 79 is a tough one because it’s not quite 80, which is my cutoff age to dose reduce. From age 80 upwards, I would use the “slow go” approach.

Answer: If VMP, treat for 12 cycles observation If len/low-dose dex, treat until PD

I would recommend continuing induction therapy with VMP for a fixed duration of 12 cycles or 54 weeks for patients who have standard- or high-risk disease. We discontinue therapy after that and observe the patient. We do not have maintenance therapy as an approved treatment option in Europe. If lenalidomide in combination with low-dose dexamethasone were administered, I would recommend treatment until disease progression.

Answer: Treat for 8-9 cycles observation

I would continue induction treatment with VMP or VCD for 8 or 9 cycles and then stop therapy and observe the patient.

Answer: Treat for 8 cycles 3 cycles consolidation LEN maint. indefinitely

I administer 8 cycles of RVD lite followed by a slightly lighter version of that regimen as consolidation therapy for another 3 cycles. Thereafter, I would administer lenalidomide as maintenance therapy.

I would continue therapy for an older patient who is not transplant eligible until disease progression. I would dose reduce if the patient could not tolerate treatment.