I typically administer 4 cycles for induction. If the patient is experiencing a good response but has not achieved a very good partial response (VGPR), I continue therapy until a VGPR is achieved. There is a good probability of achieving at least a VGPR in the majority of patients. It is a balance between obtaining a deep response and avoiding myelosuppression so that the collection of stem cells is not adversely affected.

I believe that though 4 cycles seems to be standard, a few extra cycles could be considered if the patient does not achieve the desired response. If a patient achieves a VGPR or better, that would be preferable. In our study we demonstrated that the average time to reach a complete remission was around 6 cycles.

I typically treat to best response. If the patients plateau at PR, I switch therapies. But if they attain a complete response (CR) after 2 cycles, I might continue for 1 or 2 more cycles, typically for a total of 6 cycles. With the advent of plerixafor, I’m less concerned about the effect of lenalidomide on the bone marrow.

Unfortunately there haven’t been a lot of studies to answer that question. I plan for 4 cycles of induction therapy but am willing to consider more. I would like the patient to achieve a PR prior to transplant. Historically, 4 cycles became the standard because we were administering VAD, and we had a concern about cardiotoxicity with doxorubicin.

As novel agents entered into the fray, we stuck with that 4-month modality. In the majority of patients who receive RVD, RD or CyBorD, 4 months is usually enough to reach at least a PR. But some patients may need longer therapy. Because we’re not as concerned about cardiotoxicity with the current regimens, we can consider administering more cycles.

We don’t have any Phase III data to guide us in determining what the optimal number of cycles of induction should be, so this is still an open question. The European guidelines currently recommend at least 4 cycles of induction. Data from the Spanish group suggest that the gain in terms of response is limited when adding 2 cycles. So, outside of clinical trials, 4 cycles are the standard. We do not routinely recommend 2 additional cycles but instead prefer to go straight to stem cell transplantation.

The French guidelines recommend consolidation. So if we have to use 6 cycles, we prefer to use 4 cycles up front followed by stem cell transplantation and then 2 cycles of consolidation.

We recommend 4 cycles of induction. I do not go by the level of response. I would move to high-dose melphalan therapy even if the patient had stable disease.

My decision regarding duration of induction therapy is influenced by the patient’s response and the number of cycles. The goal is to obtain the maximum response by the time you take a patient to transplant.

When using lenalidomide as part of the induction regimen, you don’t want to go beyond 6 cycles. A longer duration of therapy would affect the stem cell yield. Typically, off protocol my patients receive between 4 and 5 cycles of RVD prior to transplant and we have no problem harvesting their stem cells.

The data suggest between 3 and 8 cycles of induction therapy is effective. My own approach off protocol is to recommend induction therapy for a minimum of 4 cycles. I typically do 6 cycles, and the most I would administer is 8 cycles.