Risk Stratification Remains Key in Multiple Myeloma

Shaji Kumar, MD

While treatment for patients with multiple myeloma has greatly improved in recent years, most patients will still relapse, according to Shaji Kumar, MD. This leaves questions around the efficacy and duration of standard myeloma treatment.

According to Kumar, professor of Medicine at the Mayo Clinic, risk stratification remains an important component of deciding which treatments a patient should receive. Additionally, what should be done for a transplant-ineligible patient is not as clear as what should be given to a patient who is transplant eligible.

Currently, the standard of care for multiple myeloma is a combination of lenalidomide (Revlimid) and dexamethasone (Ozurdex) with or without bortezomib (Velcade; VRd). For patients who are transplant eligible, VRd is initiated, then 1 or 2 transplants are given, followed by maintenance therapy. Patients who are transplant ineligible continue treatment until progression.

In an interview with Targeted Oncology^TM, Kumar discussed the current standard of care in multiple myeloma, along with the need for risk stratification in this patient population.

TARGETED ONCOLOGY: What is the current standard of care in multiple myeloma?

KUMAR: The current treatments that we use for newly diagnosed myeloma, essentially, are combinations of proteasome inhibitors, even a more related drugs called monoclonal antibodies, patients who are eligible for a stem cell transplant often get induction therapy with bortezomib, lenalidomide, and dexamethasone, has a single transplant and goes on lenalidomide maintenance. If they are high risk, we try to use 4 drug combinations, including daratumumab. So, there are VRd, single or 2 transplants, and then to drug maintenance therapy. Non-transplant eligible patients often continue on therapy until progression and people with high risk disease, we tend to use VRd light, but typically try to get a proteasome inhibitor and immunomodulatory drug in there.

A couple of areas that we focused on was looking at the concept of risk rapid therapy, how can we change the treatments based on some of the commonly used risk factors? Also talking about the concept of a dynamic risk assessment because patient outcomes can vary based on how what kind of response they get, how deep response? How long will MRD negativity last and so forth. So, I think that's 1 aspect of how we will tailor therapy in the upfront setting, and maybe even in the setting of relapsed disease. I think the other concept is 1 of using multidrug combinations to provide us with a limited duration therapy so that patients can stay on treatment for a very, very long time. But it can help with both toxicities related to therapy as well as the cost of care. How can we use some tools like minimal residual disease testing, to guide us towards more scientifically defining the ideal duration of therapy for individual patient?

What are some common treatment options for this patient population?

The combinations of either a proteosome inhibitor, you have to only 1 immunomodulatory drug, lenalidomide for the newly diagnosed setting, but you also have pomalidomide for the relapsed setting. And we have a couple of monoclonal antibodies, 2 of which are targeting CD38. And there are obviously in the relapse setting, multiple different treatment options that are emerging at this point.

What are some of the unmet needs for the newly diagnosed melanoma patient population?

The key questions for the newly diagnosed patient can be to get deeper responses that can be given over shorter duration therapies, that people will have treatment-free intervals between different treatments. I think the other area that really needs to be further studied is what is the role of some of the newer immunotherapeutic agents in the newly diagnosed setting? Is there a role for chimeric antigen receptor T cells or bio specifics? Especially maybe for the high-risk patients in the newly diagnosed setting.

Do you think there is an over treatment of this patient population?

It's hard to say over treatment because we still are not curing people. So, I think until we start curing people, it's hard to say we are over treating anyone. The question is, if you can take a strategy that is curative, we certainly need to do that. And that has to be potentially more intense therapy, but potentially also more targeted therapies. So, I think by figuring out the best combinations for specific subgroups of patients, based on the disease biology, I think we will be able to cure some of these patients without necessarily, making the treatment less tolerable. But I think 1 of the key things for the future would be that we are able to do more personalized therapy so that people with specific genetic abnormalities could get a specific set of drugs that maximize the possibility of cure.

What do you want oncologist to take away from this research?

I think there are several things. I think 1 of them is the importance of risk stratification. I think we really do need to start tailoring therapy based on the underlying risk. I do want to highlight that stem cell transplant still plays a major role. I think the participation in clinical trials are clearly important as we try to learn more about these therapies and that we lose track of the importance of supportive care management for these patients. I think 1 of the key messages is that we cannot use a specific drug, or a specific combination, it's a question of figuring out what's right. And what's tolerable for the specific patient in front of you.