Strategies Explored to Enhance Treatment of Elderly Myeloma Patients

Ashley Rosko, MD

Practitioners in the field of multiple myeloma are seeking to answer several questions regarding the treatment of elderly patients, a population that, due to comorbidities, may have difficulty tolerating some of the currently available therapies.

“The thing that is important for the overall approach to older adults with myeloma is being able to focus on their quality of life and how to address both bone pain and osteoporosis, and also to meet their needs in terms of fatigue, which are the most common symptoms,” said Ashley Rosko, MD. “Balancing both the toxicities of therapy and achieving a response, as well as meeting their needs when it comes to living independently and having a good quality of life is very important.”

Studies currently ongoing are exploring varying doses of agents used to treat patients with multiple myeloma, Rosko added, as well as oral formulations.

OncLive: You lectured on elderly patients with multiple myeloma. What is important to know about this subset?

Rosko, an assistant professor in the Division of Internal Medicine, The Ohio State University Comprehensive Cancer Center, spoke on treatment approaches for elderly patients with multiple myeloma at the 2017 OncLive^® State of the Science Summit^TM on Hematologic Malignancies. In an interview, she shared insight on some of these available therapies, others under investigation, and supportive care methods being utilized for this patient population.Rosko: The bulk of therapy for multiple myeloma is nontransplant based. Not to say that transplant isn’t indicated for older adults because it is, but it is underutilized. This presentation focused on why older adults have inferior survival, the approach in terms of treatment when it comes to older adults with myeloma, and some of the supportive care methods that we’re able to better utilize for them.

When it comes to older adults, early mortality is probably the highest—there is an early death within 6 months. Part of that has to do in relation to kidney failure, underlying comorbidities, and a poor performance status. Older patients with myeloma can get better and do very well with targeted therapy. This talk focused on how we approach an older adult in terms of determining to give them 2 drugs versus 3 drugs. The majority of our focus is on being able to both achieve disease control, put disease into remission, and balance some of the toxicities. With myeloma, there are many approaches to therapy and how we do that is the art of medicine with the science that supports it.

We talked about the SWOG S0777 trial, which looked at VRD [bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone] and its benefits in terms of overall response in patients who are both transplant eligible and transplant ineligible, and the benefits of that therapy. We also looked at some supportive care methods and our history of approaching older adults with myeloma.

When I look at the history of multiple myeloma, melphalan has always been a common agent, and we talked about how that agent can still be incorporated; however, we also discussed some of the toxicities of that therapy. I also reviewed cyclophosphamide-based therapy with more novel approaches to therapy—using things like ixazomib (Ninlaro).

You mentioned that transplant might not be the best method for this population. Why is that?

What are some other therapeutic approaches that can be given to these patients?

What are the supportive care measures being used?

When it comes to relapsed myeloma, that is one of the areas that is ever changing and harder to talk about in a short amount of time. However, one of the agents that has significantly changed the landscape of multiple myeloma is the use of daratumumab (Darzalex) in the relapsed setting. We focused on sequencing that drug early in the relapse of multiple myeloma and how we can use that for older adults.Historically, transplant was targeted for a younger population; however, with better supportive care [measures] and as people are aging better, we have designed many of our clinical trials based upon the age and number of 65. However, we found that that is not a good indicator, nor a good approach, to older adults with myeloma to make these age-based decisions. We certainly moved beyond that but being able to use that therapy and targeting underutilized social demographics is relevant for this patient population, too. One of the challenges when an older adult comes into your clinic is whether or not to utilize transplant. If it is deemed that the patient is not a candidate for transplant, the question is, “Do you use 2 drugs? Which 2 drugs? Do you use 3 drugs? Which combination should be used? How do we approach that?” That is based upon 3 factors: their underlying cytogenetics, their tolerability and performance status, and some other social factors that play a role. There are travel needs and access to medications that we routinely need to accommodate for our patient population to be able to get them the best therapy. One of the hallmarks of taking care of older adults is the interface with both patients who have cancer and those who are aging. There are unique factors that come into play when taking care of older patients with cancer. At The Ohio State University, we have a Hematology Longevity clinic in which we focus on different factors related to aging, including things like physical function, pain control, fatigue, cognitive status, nutritional status, use of polypharmacy, different comorbidities, and sensory loss. That is not a routine thing that many clinicians can do in the average oncology clinic, but we think it’s important to be able to discuss the health-related quality of life for patients with myeloma.

Are there ongoing trials exploring therapies for elderly patients with myeloma?

Patients with multiple myeloma have among the poorest quality of life especially when it comes to hematologic malignancies. Being able to better optimize the factors related to aging is quite important. There are many studies that we are investigating related to older adults with myeloma, including the frontline use of daratumumab for older adults with myeloma, as well as modifications [to current therapy]. For example, recently, the standard approach to using VRd in terms of dosing has been altered a bit. There is a recent study looking at “VRd-light” in terms of real-world modifications of studies—to get doses that are more tolerable for older adults.

How can we still incorporate melphalan into this landscape?

Regarding the clinical trials that were halted exploring checkpoint inhibition in multiple myeloma, are such serious adverse events experienced in older patients?

Also, we are looking at all-oral regimens in the frontline setting. It is also very important so patients don’t have to be in clinic as much in terms of travel burden and financial burden, too. Melphalan is tricky because it’s been around [for a while] and has significant response rates that are quite impressive. [For] our older adults, it has been a backbone of therapy for many years, and, in fact, is in ongoing investigations. Recently, there was the CLARION study, which looked at the differences between bortezomib, melphalan, and prednisone (VMP) versus carfilzomib (Kyprolis), melphalan, and prednisone. The carfilzomib [arm] had more toxicity for older patients. Therefore, VMP really remains the backbone of therapy for older adults, but we are looking at VRd as well, as the approach of starting with a 2-drug regimen and work to a 3-drug regimen is also a possibility for the future.Immunotherapy in older adults is a larger question at hand. Many of the solid tumor studies are exploring the toxicities of immunotherapy. The FDA presented at the 2016 ASH Annual Meeting [a description of] some of the toxicities, and, generally, it is a well-tolerated therapy. However, it is something that is underutilized mainly because of the design of our clinical trials. There is no reason why older patients could not be included in these studies, as most of our studies are no longer age-based.