Lonial Discusses Dramatic Progress in Multiple Myeloma

Sagar Lonial, MD

The treatment paradigm for patients with multiple myeloma has changed dramatically in the past 10 to 15 years, according to Sagar Lonial, MD.

Previously, the standard of care in the induction setting was dependent upon high-dose therapy and autologous transplant. There have now been important advancements in treatment such as proteasome inhibitors, IMiDS, antibodies, and risk-adapted maintenance.

“Once you begin to introduce an antibody to part of the initial induction therapy, I think that will get us to a different plateau in terms of depth of response—achieving what we call minimal residual disease (MRD)-negativity—and having even more durable remissions for the frontline therapy,” said Lonial.

OncLive: What are some of the key recent advancements in multiple myeloma?

In an interview with OncLive at the Physicians' Education Resource 21st Annual International Congress on Hematologic Malignancies, Lonial, professor and chair, Department of Hematology & Medical Oncology, Emory University School of Medicine, chief medical officer, Winship Cancer Institute of Emory University, discussed recent advances in the field of multiple myeloma.Lonial: In myeloma, what we've done is completely change the paradigm from 10 or 15 years ago, when we used to have relatively ineffective drugs in the induction therapy setting, and were dependent on high-dose therapy and autologous transplant to do much of the work in terms of trying to induce remissions.

What we now have is very highly active induction regimens combining proteasome inhibitors and IMiDS with transplant and risk adapted maintenance that allow us to put a majority of patients into remission for between 3 to 5 years. That is just the first round of therapy.

Can you discuss the recent advancements with CAR T-cell therapy?

We also have immune-based targets using antibodies, such as elotuzumab (Empliciti) and daratumumab (Darzalex). We also have other small molecules in development that I think will help further manage how to deal with patients in the early relapse and late relapse setting. CAR T cells are interesting because it is, in many ways, a kinder, gentler way of doing an allotransplant even though it's not actually an allotransplant. If you notice, many of the side effects that we see from CAR T cells are not dissimilar from immune type reactions—also similar, perhaps in many ways, from what you see with PD-1 or other targets as well. What I think is exciting about CAR T-cell therapy is even in patients with refractory disease, whether it's ALL or lymphomas, or even in myelomas, you can get significant and in some cases durable responses.

You said that the treatment paradigm has been improved in the last 10 years, how do you think it will be improved in the next 5 to 10 years?

How do you think the FDA approval of maintenance lenalidomide will affect treatment for patients with myeloma?

At our center, we do a slightly different modification of that where we risk-adapt the maintenance therapy, but no where in there is true immune-based therapy focused. Once you begin to introduce an antibody to part of the initial induction therapy, I think that will get us to a different plateau in terms of depth of response, achieving MRD-negativity, and having even more durable remissions for the frontline therapy. In the United States, it's already being incorporated a fair amount. I still occasionally see a patient who is transplanted at an outside center and comes to us for management of disease and perhaps is not put on some form of maintenance or does not receive lenalidomide maintenance.

Is there anything else you would like to highlight?

In our experience, the only patients who probably shouldn't receive lenalidomide maintenance are the high-risk patients where single-agent lenalidomide doesn't appear to be as effective. In that case, combination with a proteasome inhibitor is, in fact, quite effective. I think in the United States that uptake has already been quite robust. In my opinion, the management of patients with myeloma, even in the newly diagnosed setting, is changing rapidly. A patient is going to want to make sure that they are partnered with somebody at a myeloma center, but it is not even necessary for that physician to give the therapy. Most of us at myeloma centers are happy for most patients to not necessarily get treated at our center, but I think we want to be involved in the management of those patients. If there are newer or more recent data sets that are released or if we have access to new drugs through clinical trials, we can make that available to those patients. Having that link with a myeloma center to be able to get the patients access to what they need is key.

The real question in my mind is if you have a CAR T cell going after B-cell maturation antigen (BCMA). For instance, in myeloma, if you had an antibody, an antibody-drug conjugate, or a bi-specific antibody, could you get that same effect by treating earlier and more often with an antibody than you can get with a CAR T cell? We don't know the answer, but we'll spend the next few years trying to address that. In my opinion, what's going to happen more routinely is the early incorporation of the immune-based therapies. Much of what we do as a standard paradigm is IMiD and proteasome inhibitor induction, single transplant and lenalidomide (Revlimid) maintenance.