The Ever-Changing Landscape of Myeloma Therapy

Transcript:Shaji Kumar, MD: A lot has changed in myeloma in the recent past, especially in the past decade. And this has touched all aspects of the disease, including the diagnosis and the treatment. More recently, the diagnosis criteria for myeloma was updated to incorporate some of those patients with very high risk of smoldering myeloma who previously were observed. That is a paradigm change in the disease because now we are willing to treat patients who have not yet developed symptoms, but have a very high likelihood of developing complications. So, we want to try and avoid that.

Now this, again, reflects a better understanding of the biology and the ability to predict who is actually going to develop myeloma in the short duration of follow-up. We also have significant advances in terms of the particular therapies we use. We have several new classes of drugs that have become available within the past few years, the most exciting of them being the monoclonal antibodies, which were approved only within the past year.

The new classes of drugs that have become available have, in turn, allowed us to create combinations that are highly effective. And this results in responses that are deeper than what we have seen with the previous medications, as well as the stem cell transplant. So, now we have new drugs and new combinations that can be used in conjunction with transplant, where applicable, to give very deep responses. And not only that, we also have data supporting prolonged use of some of these therapies to try and keep the disease under control for long periods of time. Now, because of these deeper responses, we also have had to update the response criteria, which was done about a year ago. We’ll be introducing minimal residual disease testing as part of the response criteria. Minimal residual disease negativity was not something that we had typically thought about in myeloma at least until recently.

Now with the new therapies, we are able to obtain an MRD-negative status in a substantial number of patients, even in patients who have relapsed myeloma. This, we believe, would be the first step toward actually curing this disease in a proportion of patients. Obviously, we need to do more studies in order to further answer, is there a particular combination that could help us do that? Is it the duration of treatment that would help us do that or is it early intervention in patients with smoldering myeloma that will actually help us cure the disease?

So, having all these new drugs in myeloma is clearly a great advance, but it also poses a significant challenge for people who take care of myeloma. Now, the vast majority of the oncologists who take care of myeloma patients don’t necessarily take care of a large number of these patients. It is particularly challenging for them when you have so many different new drugs that have come to the market, and particularly the combinations that have been developed based on these new classes of drugs. The challenge that the oncologists face today is, how do we select a particular therapy for a particular patient? Now, clearly, we have made some progress in terms of identifying how a particular class of drug may be beneficial for a group of patients. Particularly in terms of the high-risk patients, we know that proteasome inhibitors have a critical role to play in those group of patients. So, combinations based on proteasome inhibitors are particularly important for those groups of patients.

We also know that the older patients don’t do as well. So, we also have incorporated into guidelines how to adapt a therapy for older patients. Similarly, patients who present with particular types of complications—for example, renal insufficiency—may need some change in the treatment incorporating certain agents, while not using others, to get the maximum benefit in terms of not really just controlling the myeloma, but also maximizing the chance of reversing some of those renal failure-type complications.

I think the important thing for the practitioners is to use some of the guidelines that are being developed, especially from the Interaction Myeloma Working Group. They have come out with guidelines that are targeted toward adapting the therapy for certain groups of patients based on their presenting characteristics. But equally important is to get a better sense of what are the types of toxicities these drugs have. Now, some of the toxicities are fairly similar with all the cancer agents—a drop in the blood counts or reactions to monoclonal antibodies—which most people are familiar with, and it’s easy for them to manage those. But these drugs can also have some specific toxicities. For example, peripheral neuropathy with bortezomib needs a different approach, and it’s important for the practitioners to be aware of how to modify the doses or how to react to particular toxicities that you may see from these drugs.

One of the key aspects of taking care of myeloma patients is the team approach. Obviously, not every myeloma patient can come to a large tertiary welfare center to have their myeloma taken care of. So, I think it’s very important for the academic centers and the myeloma specialists in academic centers to collaborate with primary hematologists and oncologists who practice in the community so that patients can get the best care in the community that they live in.

And there are different ways of doing that. I think it’s important for most of these patients with myeloma to be at least seen by a specialist in the beginning so that you can chart out a plan of treatment. It’s important for them to be seen in the larger centers for consideration of stem cell transplant, if they are eligible for that. And it’s also important to maintain that relationship on an ongoing basis, maybe having them see the specialist at least once a year so that when they come to a problem, they can get the help of the specialist. Later on in the course of the disease, when they have become refractory to some of the commonly available drugs, they also have access to clinical trials. So, I think it’s very important to maintain that team approach right from the beginning, from the time of diagnosis all through the journey of dealing with myeloma.

Transcript Edited for Clarity