Drive treatment decisions and predict long-term outcomes in multiple myeloma



After completing the initial combination therapy for multiple myeloma, maintenance therapy can help a patient maintain a response to treatment and potentially achieve minimal residual disease negativity, which is key to functional treatment of the disease. disease, said an expert.

In addition, screening for minimal residual disease in patients with multiple myeloma can help make treatment decisions and lead to a more tailored approach, said Dr. Dickran Kazandjian, professor of medicine at the Sylvester Comprehensive Cancer Center / University. from Miami, Florida, to the CURE® Educated Patient® Multiple Myeloma Summit.

CURE® also spoke with Kazanjian to learn more about the importance of learning about maintenance therapy, new therapies on the horizon, and why aiming to achieve minimal residual disease negativity can improve outcomes. long-term.

CURE®: Why do you think it is important for patients to know about this topic?

Kazanjian: It’s really important because some patients, after their initial diagnosis and the start of treatment, can do very well. When they are doing very well, usually after the initial combination therapy, we put the patients on maintenance therapy, which is like a lot of other chronic conditions like hypertension. Lenalidomide (Revlimid), which is the main medicine we use for maintenance treatment, is a pill, so it becomes very convenient.

In patients who were maybe four or five years after starting maintenance therapy, the question arises, “Well, there are no signs of myeloma during this time.” Do I really have to keep taking this pill? I think that’s a very difficult question to answer. At first, most patients don’t realize and are surprised when I tell them that after the initial combination therapy, they will likely need a maintenance strategy indefinitely. When they ask me for how long it doesn’t sound very good because the standard answer is “indefinitely”. It is important that patients understand why we are doing this. I think the evidence behind the administration of maintenance therapy (Revlimid), for example, is one of the strongest, because it not only helps patients not to progress further, but has also been associated with it. to a survival advantage in a number of previous trials. However, these trials focused on the entire patient population and did not include patients who can achieve minimal residual disease negativity.

In your presentation, you talked about some innovative therapies. Which do you think are the most promising in this area?

Quadruplet-based therapies which essentially take precedence over our triplet therapies. But not all quadruplets are the same. When you use a really well-established triplet backbone for a newly diagnosed (patient), at least in the US, and add a very effective fourth myeloma drug, these are the quadruplets patients need to think about.

It’s a bit abstract, but more to the point, patients really need… to receive a proteasome inhibitor and immunomodulatory drug upstream and add on top of that… an anti-CD38 monoclonal antibody. Most of the studies have been done with Darzalex (daratumumab), which is completely accessible. I think (Darzalex) has a lot of data to support itself in myeloma. (In addition), the company has worked on refining it, so we no longer do dosage based on weight; it is a fixed dose for all patients. (Also, now) patients can receive it subcutaneously.

The other thing that has changed a lot is the risk of infusion reactions, which was the major problem with (Darzalex), and now we all know how to give prophylactic anti-reaction drugs well. The subcutaneous route (administration) itself decreases the incidence of infusion reactions.

It is not the only anti-CD38 monoclonal antibody. Another catching up is Sarclisa (isatuximab). And so that’s another topic to watch out for, along with a few less common ones that are earlier in the drug’s development.

Can you explain what the minimal residual negativity of the disease is?

Minimal residual disease negativity means different things in different disease settings. In multiple myeloma, minimal residual disease – we call it MRD for short – the negativity is based on the bone marrow tissue. Traditionally, when we follow multiple myeloma to see how the patient is doing during treatment, either in terms of response or, conversely, progression, we usually look at it from the blood. We are lucky, we have a pretty good blood substitute (m proteins and serum free light chains), unlike many other tumors. Even lymphoma, which is a close cousin, you really have to do some imaging.

But we are fortunate to have a blood test to assess the response. This answer does not go further; it’s a concept where the deeper you look, the more you can find. If you can’t find (no affected cells), it gives you a deeper response (to therapy). What it is in myeloma is that your blood no longer shows monoclonal proteins or serum-free light chains, which are surrogate markers for myeloma, and on the bone marrow biopsy, traditionally we let’s look at how many plasma cells and whether they are monotypic or not.

What is really important for patients to know that not all MRMs are the same. To be able to say that you are MRD negative, you have to know what the sensitivity or detection level of the test is. And so in myeloma, that means you need your test to be able to prove that after you’ve looked at 100,000 normal cells, none of them are abnormal. So our current test for MRD is flow cytometry, which gives us that kind of sensitivity. We also have next-generation sequencing platforms, which do not necessarily replace, but are complementary in some cases. And that was cited to give a sensitivity of one in a million to be able to detect that much. But these are general averages, and each patient sample technically has its own level of detection sensitivity. This is what is gaining momentum.

It’s not necessarily a new test now. We were talking about it five or ten years ago. It is now incorporated slowly. What patients need to know is that at least the next generation sequencing test… performed by Adaptive Biotechnologies is FDA approved. This means that CMS and other payers are more likely to cover the costs, which you can imagine is probably quite expensive. This is the way to go.

On the other hand, what do you do with this information? I can tell you all of my patients want to know if they are MRD negative or not, those who googled it and found out about MRD. It is something that you want to achieve.

In many cases, if you don’t reach MRD negativity, we don’t necessarily know what actions we might take. For example, does that mean we need to change therapy? Maybe we are on the same therapy for longer? To give a simple example, if someone has newly diagnosed myeloma, we put it under (Velcade, Revlimid and dexamethasone) or (Darzalex, Kyprolis, lenalidomide and dexamethasone), the common practice for treatments for newly diagnosed myeloma. . And after two cycles, if you did a bone marrow biopsy and the patient was not MRD negative, I don’t know what that would mean, which means you could easily give four to six more cycles and that they could convert at this point. In fact, this is more the exception than the rule, but it does occur when patients have converted to MRD negativity while on maintenance treatment, i.e. after the initial combination. of three drugs.

What advice would you give to patients and their caregivers?

I think my biggest advice is that a lot of these topics are very complicated. I have spent many years focusing on this. The most important thing for patients is to be able to find a doctor they trust, an expert in myeloma, and make them journey together. … And I think there are different levels of understanding. Generalist oncologists can figure it out, but it’s really not the same level. And although it is the second most common blood cancer, blood cancers are rare. So, it’s really up to everyone to reach out.

Of all the negative things, at least one of the positive things with the COVID-19 pandemic is (that it) has made telemedicine more accessible. And now a lot of people, including us here at Sylvester, are offering that to patients. So even if it’s a one-off shot or a once in a while to get a second opinion, I think it’s probably worth it.

This interview has been edited for clarity and brevity.

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