This content was developed by ONS, Beth Faiman, PhD, CNP, and Kimberly Noonan, NP, and is sponsored by Amgen. Faiman and Noonan received no payment for their participation.
Finding the right treatment pathways is essential, and this is perhaps most true in the treatment of uncommon, complex, and incurable diseases. Multiple myeloma (MM) is a cancer formed by malignant plasma cells, and more than 30,000 new cases will be diagnosed in 2016 with more than 12,000 deaths estimated. Although MM is incurable, many treatment pathways are available to manage the disease.
Kimberly Noonan, NP: To start, what is your impression of the MM disease state?
Beth Faiman, PhD, CNP: Before we had newer drugs and treatment therapies, when I started taking care of patients in the mid-1990s, everybody was treated only through a transplant or chemotherapy. Nowadays, such a plethora of treatments are available. And that is one of our challenges: when people are newly diagnosed with MM, there is no clear standard of care. It is hard for people to make decisions about their treatment. But it is promising, at time of diagnosis, to be able to say, “Multiple myeloma is incurable, but it is highly treatable for most patients.”
KN: Yes, patients can now live an awfully long time with MM; this is a very exciting time to be involved with the disease. At Dana-Farber Cancer Institute, we have seven physicians who work with MM alone. If you were to line them up, they may have a different perspective about treatment in terms of upfront transplant versus delay transplant until relapse. What do we start off with? When do we put people on a trial? Patients have plenty of options when they are diagnosed with MM today. How do you help them understand MM and its treatment?
BF: In Cleveland, OH, where I’m located at the Cleveland Clinic, we have distinct seasons. I find it helpful to use the analogy of these seasons. I give my patients the example of the leaves in the fall—how they go away. Then winter comes and you think the leaves are just gone, but then they will inevitably come back in the spring. I use that analogy to try to explain to the patient and caregiver that MM is something that could can back. It is incurable but treatable, as long as we suppress it so that no significant problems will come back at relapse.
KN: What are some of the drug therapies that are used with your patients? What is your first, second, and third line of treatment?
BF: As you said before, if you lined up all of your seven myeloma specialists at Dana-Farber, you would get different opinions on how best to treat myeloma. So there is not standard of care. But, at my institution, we actually have a care path for anybody who comes in with a “standard” type of myeloma. Standard myeloma means that they do not have any major genetic changes on the genetic profiling panel, and they do not have any very “bad” FISH—the fluorescent in situ hybridization translocations. These patients are usually offered lenalidomide and dexamethasone, with the option to have an early or delayed transplant. If an individual has high-risk disease or renal failure at diagnosis, then that individual would be offered a bortezomibbased regimen, plus or minus transplant. So that is our standard of care. And much like the Dana-Farber Cancer Institute, we, at Cleveland Clinic, have a lot of clinical trials for newly diagnosed and relapsed patients. So while we mix and match treatments, many patients will go from one drug on to the next. Based on the recent results of clinical trials such as the ASPIRE trial, which studied carfilzomib, lenalidomide, and dexamethasone in patients with relapsed myeloma, some patients will receive the combination earlier on in therapy rather than waiting until the end of therapy. While treatment of the myeloma is important, it is also important for nurses to remember supportive care throughout the disease trajectory. Supportive care includes giving bisphosphonates for people with bone disease, administering antivirals if patients are on proteasome inhibitors such as bortezomib and carfilzomib, and preventing long-term side effects by conducting health maintenance, such as looking at blood sugar readings, monitoring blood pressure, and encouraging a healthy and active lifestyle.
KN: In our treatment protocols, I have to think about the National Comprehensive Cancer Network guidelines; when you look at what they are suggesting, it is all over the place. We have a trial at Dana-Farber in which we put people on a protocol with RVD upfront—so lenalidomide, bortezomib, dexamethasone—and then participants are randomized to receive a transplant or receive the pivotal eight cycles of RVD followed by maintenance therapy of lenalidomide to see which group does better. Now, we’ve been doing this protocol since 2009 and we are still enrolling. The jury is out in terms of an upfront transplant versus standard therapy, but I do see that we are using an awful lot of lenalidomide, bortezomib, and dexamethasone upfront followed by maintenance therapy. This trial was a collaboration with French researchers of the Intergroupe Francophone du Myélome group, and we are excited for the results to come out.
BF: It is nice that we have all of these options for second and third lines—even fourth and fifth lines coming up. Last year, at the American Society of Hematology conference, huge developments were reported, such as the monoclonal antibodies (such as elotuzumab), CD38 antigens, autologous stem cell treatment, or the proteasome inhibitors (such as carfilzomib).
KN: But just in terms of those two—monoclonal antibodies and the new proteasome inhibitors—what therapies do you find are promising going forward?
BF: First, I am just as thrilled as you are. These drugs are possible game-changing and highly effective drugs in the treatment of myeloma that we’ve been waiting for all these years. The monoclonal antibodies are for a specific approach, so they are not going to be acting like chemotherapy directly attacking the myeloma cells, but they affect the environment around the cancer cells and the proteins that are attached to the cells.
And as I mentioned, we mix and match drugs, sometimes at lower doses to give a maximum benefit and treat myeloma cells from different areas. So I think the monoclonal antibodies represent very promising drugs.
Another drug, an oral proteosome inhibitor called izazomib that is going to be coming out early this year, is showing promise in clinical trials. We should mention the histone deacetylase inhibitor panobinostat, which is FDA approved for the treatment of relapsed myeloma.
KN: Also, the inhibitor carfilzomib. What we are hearing is that there may be an increase in cardiac issues. We are doing echoes before treating people, and we are really not finding too much of an issue—I think the data is somewhere around 8% to maybe up to 10% with the dosing of about 27 mg/m2. But I think it is very well tolerated. When we have come across patients who have had cardiac issues, we’ve been able to cut back on their fluids, but also just maybe even lower the dose to address any bloating or edema; people tend to respond to that, and we are able to get more mileage out of carfilzomib.
When you think about this disease a decade or 12 years ago, we had no hope; now, we have a lot of hope and a lot of options. And I hope that these drugs added to other protocols could give people a complete response and maybe even cure.
BF: Yes, that’s what we’re hoping for. So, in thinking about future treatments, are there any other developing or current clinical trials that you’re finding exciting where you are working?
We’ve mentioned the monoclonals and the results with that recent data. There is also another oral proteasome inhibitor, oprozomib. There is a frontline trial in which we have several nontransplant older adults. So it tends to be older individuals using oprozomib, but it is given in combination with cyclophosphamide and dexamethasone, and we have quite a few patients who are tolerating it very well, and they are not having any major treatment-related side effects. So, while we are sharing with you exciting news about drugs that are hopefully going to be approved by the FDA for use in our institutions fairly soon, I don’t think oprozomib is going to be that far away either.
KN: Oh, I agree. I also think the PD-1 inhibitors are just a huge area that is about to explode.
BF: Yes—those will be game-changers, hopefully. It is a tough disease to have, but at least there are plenty of options, more excitement, and more to offer our patients.
KN: In thinking about potential issues for patient groups, what about the treatment of older adult patients with multiple myeloma? Do you find that you treat them with the same protocols or with the same dosing?
BF: Treatment of multiple myeloma in older adult patients has changed arguably more than any other disease group in the past 20 years because everybody used to get standard chemotherapy. Now, we have a plethora of new drugs to fight the cancer, and two major studies in the past five years have shown new ways to treat MM. One study was the VISTA trial, which compared bortezomib, melphalan, and prednisone to melphalan and prednisone alone. In this trial we saw a big improvement in progression and survival among patients who got the bortezomib in combination with oral melphalan and prednisone versus the group who only received oral melphalan and prednisone and bortezomib. And we also had the FIRST trial, which looked at continuous lenalidomide and dexamethasone in older adult patients who could not receive a transplant.
In both trials, the groups that benefited the most were the very older group, those aged over 75, especially in the latter trial, the FIRST trial, because we could give lower dose of steroids and we could give lower doses of lenalidomide. The patients were able to tolerate the treatment much better and stay on therapy. So when you ask how treatments change for older adult patients, in many cases they will get the same drugs as their younger counterparts, such as lenalidomide and bortezomib, but they are also able to stay on the treatment longer, and often with less side effects, because lower doses of effective agents.
KN: We are probably going to see a lot more data come out of some of the RVD lite protocols, using combines lower doses of lenalidomide, bortezomib, and dexamethasone. I think that it is very well-tolerated by older adults for a longer period of time, and we are going to generate a lot of information from that as well.
BF: I do want to talk about survivorship because, in the past, we have not been able to talk about survivorship with MM. I was recently in Rome at the International Myeloma Workshop, and we were discussing how the clinical trials can’t look at overall survival as progression-free survival because patients are living so long.
It is important to have conversations about options—I think patients like to know that there are other options if their treatment isn’t working or isn’t working as well as we’d like. So I always like to intermittently have that conversation on follow-up visits of what is new in myeloma and what drugs that patients might be candidates for in the future.