Maintenance Therapy in Multiple Myeloma

Transcript:Maria Victoria Mateos, MD, PhD: Lenalidomide is becoming a standard of care after transplant for young, newly-diagnosed myeloma patients because lenalidomide has demonstrated duplicating the progression-free survival in these patients. In addition, in a large meta-analysis recently conducted in 2 phase III randomized trials, lenalidomide as maintenance also demonstrated prolonging the overall survival. In the nontransplant-eligible myeloma patients, lenalidomide and dexamethasone as continuous therapy is one of the standards of care. And I would say that tomorrow, probably, lenalidomide and dexamethasone as continuous therapy, will be a backbone to which other novel agents are going to be added. But my answer is definitely yes, lenalidomide is becoming a standard of care in both transplant and nontransplant-eligible myeloma patients.

Shaji Kumar, MD: The concept of maintenance therapy has increasingly taken a foothold in myeloma, and we have multiple studies showing that lenalidomide maintenance after stem cell transplant clearly improves outcome. There’s a recent meta-analysis which clearly showed that there’s an improvement in the overall survival when patients got lenalidomide maintenance after stem cell transplant, and that has become the standard of care in the posttransplant setting. But there’s still a lot more work that needs to be done to define how long the maintenance needs to be continued, and whether we can build up on the maintenance strategy by adding more drugs to the lenalidomide.

We know from some of the European studies that bortezomib maintenance is also a reasonable approach, and has shown some benefit in the high-risk patients in particular. This is important because the subgroup of patients who did not benefit from lenalidomide maintenance are patients with high-risk myeloma. So, clearly, we need to do something different for patients with high-risk myeloma, and the answer might be a proteasome inhibitor-based maintenance therapy in those patients.

Now in the known transplant setting, it’s a little bit more of an open question. We know that from the first trial, which used lenalidomide continuously until disease progression, compared to 18 months of lenalidomide/dexamethasone, there was an improvement in the progression-free survival, but no distinctive improvement in the overall survival when you compared the indefinite versus 18 months of lenalidomide. There has been some meta-analysis of European trials that suggested that a continuous therapy is better than a fixed-duration therapy. However, I think in the known transplant setting, we still need more information to say continuous therapy is better than stop-and-go-treat after disease comes back versus discontinuing the treatment.

Maria Victoria Mateos, MD, PhD: Lenalidomide can be considered one of the standards of care to be used as maintenance in transplant-eligible myeloma patients. However, lenalidomide is effective in most of the different subgroups of patients with some exceptions. For example, patients with ISS 3 or patients with high-risk cytogenetic abnormalities do not benefit from lenalidomide as maintenance. In addition, we are going to have the results of phase III randomized trials in which other novel agents are being evaluated in this setting. Proteasome inhibitors, like ixazomib of oral administration, are being evaluated in a couple of phase III randomized trials. I can envision that in the future, probably the combination of the oral proteasome inhibitor plus lenalidomide as an immunomodulatory drug can be of great benefit for patients after transplant to be used as maintenance therapy.

Shaji Kumar, MD: In the maintenance setting, the key aspect of the drug to be used is that it should be convenient, so preferably it has been oral drug so patients don’t have to come back to the clinic every so often. Because the whole concept of getting patients to a transplant is, and getting the disease into a deep response, to get patients back to a normal lifestyle. So, if they had to keep coming back to the clinic every week or every other week, then it doesn’t solve the problem.

I think one of the important things is to be able to use oral medications. If you have to use an IV medication, use that in a very less frequent fashion, maybe once a month. So, lenalidomide, from that sense, is a good drug because it’s a pill. Patients can take it at home. One of the disadvantages with bortezomib is that patients will have to come back once every other week, at least based on the studies that have been done in terms of a maintenance approach.

Now one good thing is, we do have ixazomib, which is currently going through clinical trials in the maintenance setting. We know it is effective. It has been studied both alone and in combination with lenalidomide in newly diagnosed patients, also relapsed patients, and it is an effective drug. In the maintenance setting, it would be an ideal drug because it’s an oral drug. We know from the newly diagnosed studies that it can be given continuously over a long period of time without any cumulative toxicity. So, that makes it, again, a drug that is amenable to a maintenance setting. Obviously, we need the data. There’s the phase III trial that has completed accrual, which hopefully will give us more information on that.

The monoclonal antibodies certainly are another option, especially since we know that daratumumab can be given once a month on a long-term basis with very little cumulative toxicity. So, that is another drug that potentially could have a role in the maintenance setting, and obviously, we need data.

Transcript Edited for Clarity