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Expert Sheds Light on Role of Combinations, Transplant in Myeloma

Angelica Welch
Published: Friday, Oct 27, 2017

Jayesh Mehta, MD
Jayesh Mehta, MD
With a plethora of combinations available and being explored in the multiple myeloma landscape, researchers are assessing the right number of drugs to use in combination regimens.

While data have shown that triplet regimens are more beneficial than 2-drug combinations in the relapsed setting for patients not undergoing transplantation, Jayesh Mehta, MD, said that the added benefit of 4-drug regimens remains unclear.

During the 2017 OncLive® State of the Science SummitTM on Hematologic Malignancies, Mehta, professor of medicine (hematology and oncology), Feinberg School of Medicine at Northwestern University, discussed combination therapies in multiple myeloma, as well as the continued importance of stem cell transplant.

In an interview during the meeting, Mehta shared his insight on the backbone of lenalidomide (Revlimid) and dexamethasone in combination therapies, the use of checkpoint inhibitors in multiple myeloma, and the stable role of stem cell transplantation in these patients.

OncLive: Please provide an overview of your lecture on combination therapies in multiple myeloma.

Mehta: We reviewed the role of combination therapies, and the fact that 3-drug combinations seem to be better than 2-drug combinations in relapsed myeloma. [It is unclear whether they are better] in patients who are not going to be transplanted. What is also unclear is whether 4-drug combinations are better than 3-drug combinations. Essentially, the whole point is, do we want to give multiple drugs at the same time, or give a small number of drugs first and then add in or substitute drugs later in the course of the disease? We don’t know the right answer to this. 

What we do know is that when you have multiple new agents in the same combination, the cost becomes staggering. You have combinations that could cost as much as $400,000 a year. The health systems cannot survive such expenses.

What are the factors that you take into consideration when deciding between combination regimens for patients?

Patient age, what treatments they have had in the past, what their organ function—specifically kidneys—is like, what their blood counts are, whether they have undergone a stem cell transplant, and convenience for the patient. 

Will lenalidomide and dexamethasone remain an integral part of combinations for myeloma moving forward?

I am not sure that will be the case. The major reason that lenalidomide and dexamethasone is the backbone is because it is one of the major combinations in which data exist. The specific label was on lenalidomide and dexamethasone in the relapsed setting. However, there are other active combinations or active drugs that can be used. The attraction of lenalidomide is in the activity, but the proteasome inhibitors are also very active.

Are there any exciting newer combinations that are being studied? 

Combinations that might include an element of immunotherapy might be interesting. Trying a drug such as elotuzumab (Empliciti) early in the course of the disease, when the immune system is not knocked out, may be interesting to use. Drugs such as lenalidomide and pomalidomide (Pomalyst) do not compromise the immune system, particularly T-cell–mediated immunity—the way that daratumumab (Darzalex) and the proteasome inhibitors do. Focusing on drugs that don't compromise the immune system that much would be quite fascinating. I'd love to explore the combinations of elotuzumab and lenalidomide in frontline myeloma.

There is some interesting stuff worth looking at. The problem is that the early pathway in myeloma is already pretty well established. By the time patients come in after relapse, I don't know that you have the luxury of time on your side to explore regimens that try to avoid immunosuppression by excluding drugs like proteasome inhibitors, steroids, and daratumumab. 

There has been a lot of buzz about daratumumab. Could you share your insight on this agent?

I have not been very impressed with daratumumab when it is used as a single agent as labeled. When we use it with high doses of steroids, the response rates have been better. When used in combination, the response rates have been better. It is a tough drug to use due to the fact that it causes myelosuppression.

It causes a lot of reactions and is associated with a lot of infections. However, we use a lot of daratumumab and all of these drugs because we have a very large population of patients to look after, and I see the kind of adverse effects that we used to never seen before.

There have been a few holds in multiple myeloma trials recently. What are your thoughts on the potential of pembrolizumab (Keytruda) and nivolumab (Opdivo) in these patients?


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