FCS’ Bailey Discusses 4-Drug Regimens, Use of MRD in Multiple Myeloma

Ray Bailey, BPharm, RPh, is the senior vice president of pharmacy services for Florida Cancer Specialists (FCS) Pharmacy Services operations. In this role, Bailey oversees intravenous and oral medications and is responsible for financial management, business development, new drug access, purchasing contracts, and overall formulary management. Bailey joined FCS in 2008 as pharmacy manager and was later promoted to director of pharmacy for the FCS Oral Oncolytic Pharmacy (Rx to Go). Bailey spoke with The American Journal of Managed Care® (AJMC®) just after the conclusion of the 63rd American Society of Hematology (ASH) Meeting & Exposition, which took place December 11-14, 2021. This interview was edited lightly for clarity.

AJMC®: Could you describe the health care resource utilization of a patient with multiple myeloma. What are the drivers of costs for this disease state?

Bailey: It’s the drugs, for sure. Pretty much for all the patients, whether they’re transplant eligible or not, when you get into relapsed/refractory disease, they’re going to be on triplet [or] quadruplet therapies now—so a lot of cost is the drugs.

As I review this, there’s not a lot of opportunities [for savings]. Looking at overall cost, there’s not much of a difference between the regimens in myeloma therapy. So absolutely, drug costs drive multiple myeloma [resource utilization] in our practice.

AJMC®: How does the economic burden change as patients start progressing toward that relapsing/remitting multiple myeloma stage, as opposed to the initial onset of the disease?

Bailey: It depends on whether the patients are transplant eligible or transplant ineligible. A lot of these patients are seeing anti-CD38 [therapy] early, in the front line. So when they progress, they may see it anti-CD38 again, or not. We’re currently looking at our formulary pathways in that space and trying to define and tease out [what comes] post anti-CD38. But the other therapies are as expensive or more expensive; these are usually more novel, newer drugs [and] can be more costly.

The patients are going to be heavily pretreated. They’ll move down through the different lines of therapy; now we’ve got anti-BCMA CAR T [immunotherapy]. We’ll have bispecific [antibodies] next year, probably. So, I would expect [for] those patients, as they live longer, [that] those costs the will continue to escalate.

AJMC®: How would you say that the cost of multiple myeloma compares with other oncology priorities that you’re treating, such as breast cancer, for example?

Bailey: I don’t think we’ve defined per se, by disease state, which is the biggest driver. We are a value-based organization; probably 70% of our patients are in the value-based OCM [Oncology Care Model]. We’re not sure what’s going to happen next year with the OCM. But from our OCM data, it looks like multiple myeloma is one of our biggest drivers of cost. I can’t say for sure that it’s the biggest driver, because you’re right—there’s a lot of innovation, a lot of disease states with a lot of expensive therapies—but probably multiple myeloma would be at the top or top 3, for sure.

AJMC®: Given that cost, what is your strategy for evaluating treatments for value? How do you gain value out of what’s coming down the pipeline in multiple myeloma and what’s currently being used to treat these patients?

Bailey: So, we’re a NCCN [National Comprehensive Cancer Network] practice; we follow NCCN guidelines. As I mentioned it earlier, we have a formulary navigator pathway [in which] we look at each individual’s disease state and we try to assign value to individual regimens where there may be multiple choices. We’ll crunch the numbers on the total cost and compare that to the NCCN category, and then we may have a preferred regimen in a specific line of therapy by disease state, or a couple that we’ve identified as preferred based on the way we look at it through our [pharmacy and therapeutics committee], which is efficacy first, side effect profile, and then value.

We try to assign a value to that specific regimen. It [involves] a lot of different things. First, for the total cost of care: We are value based, [so] we’re looking at what is that cost for that line of therapy. And we’re looking at other things that create value for the practice as well. Those all come into play on that third component, which is third after efficacy and side effect profile.

And then, obviously, our doctors are free to choose whatever they think is best for that individual patient. If you’re looking at something like multiple myeloma, that’s going to include [whether the patient is] high risk, cytogenetics, comorbidities—things like that come into play. You can’t specifically say “Well, you should use this regime,” because every patient should be individualized. And that’s what our doctors do.

AJMC®: Keeping that in mind, are there specific clinical outcomes, such as efficacy or the safety profile or overall survival rates, that are impressive, that demonstrate high value? And are there nonclinical outcomes, such as whether a drug is competitive on cost or participation in a value-based agreement, that you find to be of high value personally when you’re evaluating these drugs?

Bailey: Multiple myeloma is very complex. I can say in other disease states, it’s a lot easier to do this. If you look at all the different oncology disease states, when we’re applying value-based metrics and parameters to it, it can be very easy, kind of cut-and-dry. But with multiple myeloma, it’s very tough to do.

We’re seeing that perhaps there’ll be some opportunities for generics, where we could assign some value there. Bortezomib has been off patent for a while, but we can’t use it sub-Q [in a subcutaneous] formulation. So we’re going to have an opportunity with a sub-Q generic version of bortezomib in probably April or May of [2022]. That will help us assign some value. Then, I think lenalidomide is supposed to be available as a generic in the first quarter of [2022]. However, because of the complex REMS [Risk Evaluation and Mitigation Strategy], it looks like it’s just going to be a small percentage of the total amount. So there may be some opportunities for [lenalidomide] generics to create some value there.

AJMC®: You mentioned formulary pathways previously. And I’d like to speak more about that. How are you using clinical pathways, formulary navigators, and clinical decision support tools to support selection of some of these therapies that we mentioned? Are these therapies that we know gain value for patients—that have great efficacy, safety profiles, and good outcomes as a result?

Bailey: We haven’t gone the way of pathways yet….We have developed what I think is a very innovative tool. It’s a proprietary tool—I call it formulary navigator—where we put an incredible amount of work into looking at all the disease states, and then creating based on line of therapy–specific regimens for our practitioners, with [National Comprehensive Cancer Network guidelines] NCCN as the backbone. And by line of therapy. Once we built that, we have a team of clinical BCOPs [Board Certified Oncology Pharmacists] that manages that whole catalog of different disease states and decision support tools that we put in. We update it, because the NCCN is changing constantly, as you know.

What we do is we commit to our practitioners that we will change it at least monthly. If some practice-changing data come out, we may update our formulary navigator more often, but we’ve committed to at least monthly changes [based on] NCCN in our formulary navigator, which is a lot of work. Some people may not realize how much energy and effort it takes to just keep up with NCCN.

AJMC®: I think you made a great point. I think I was looking for some updated guidelines just recently, and it looks like the NCCN is posting nonstop on some of these cancer oncology disease states. But with that in mind, how are you using these tools specifically for the anti-CD38 therapies for multiple myeloma?

Bailey: As I mentioned it earlier, we’re seeing a lot of [daratumumab] for nontransplant-eligible patients, front line. So those regimens are very prominent. And I think there’s a lot of uptake inside of our practice, particularly, for nontransplant-eligible patients, for sure. But they’re probably highlighted more in the relapsed/refractory section of our formulary navigator for multiple myeloma.

I guess the big question out there is sequencing between the 2 anti-CD38 therapies that are there. I guess there is some data to support sequencing the anti-CD38 after a 6-month period. I don’t typically make those kinds of judgments for our patients, but I do know, there’s evidence there. We are currently in the process of defining in that relapse/refractory section, post–anti-CD38, and trying to define and tease out regimens to use post–anti-CD38. I think that will be valuable. But that’s because the NCCN gets very complex and convoluted when you’re looking at relapsed/refractory. And if we can do anything to guide our physicians there or provide them with some decision support tool, we want to do that for them.

AJMC®: You make a great point, that the NCCN guidelines end up reading a bit like a huge tree, rather than a straight line for a physician. So anything to guide them is very valuable. I think you mentioned previously the use of anti-CD38 therapies up front, then in newly diagnosed multiple myeloma, using something like an anti-CD38 plus RVd [lenalidomide, bortezomib, dexamethasone] combination. There are 2 of them—daratumumab and isatuximab. Both had some recent trial data in this patient population. How do you evaluate value of a 4-drug regimen? What goes through your mind when considering who should be taking a 4-drug regimen? Or are you still waiting for more data to better support their use?

Bailey: There was a lot at ASH specifically around using the 4-drug regimens for induction transplant consolidation. I think 2 that you referenced had 24-month maintenance with MRD [minimal residual disease] surveillance. So that’s amazing. I hope that takes hold; of course, it’s going to have to make its way into the NCCN guidelines. I think that we already have 4-drug regimens in our formulary navigator for transplant-eligible, high-risk patients. I think that’s [level] 2A NCCN now, so it’s there. But this whole novel idea of fixed duration maintenance afterward with MRD surveillance—I think is fascinating. And I hope I hope that the data bear out.

AJMC®: I think the use of MRD and multiple myeloma is particularly innovative. Both trials I mentioned were using MRD negativity to measure their outcomes. Can you speak some more about this? How does your practice use MRD? What do you think of this outcome? What does it mean for patients, for physicians, and for oncology practices?

Bailey: As I said, I don’t make clinical decisions, but I’m around oncology a lot. I think even if you talk to multiple myeloma experts, they don’t always have the same opinion on using MRD. And I think it’s probably the same case with our physicians. We do use it, it’s available, they can order it. You know, I think it applies also to the [chronic lymphocytic leukemia] space. We put footnotes in our formulary navigator for multiple myeloma in CLL, considering MRD testing, so I don’t think it’s taken hold yet, but it’s there. And if some of the data from ASH pan out, then I think we’re going to see more of it for surveillance after a fixed-duration maintenance. Then it could make sense, particularly for lower-risk, or for patients with 1 risk factor.

AJMC®: It’s an area of innovation. I’ve seen some studies that involve sparing maintenance in patients based on MRD negativity. I think some institutions in the United States are using it that way. Are any other ways that MRD might be being used to advance our cancer care, whether it be multiple myeloma, or, as you mentioned, CLL?

Bailey: I’ve seen some pilots from payers around the country where they’re keenly focused on MRD testing. And they’re doing pilots as a value-based option for practices that want to participate, where they’re looking at doing MRD surveillance; fixed-duration maintenance is where there could be cost savings to the system. And there could be value there. I know we’re going to see more of it the future. I just don’t think it’s prime time yet, so to speak.

AJMC®: Is there anything else you’d like to add?

Bailey: Along the theme of MRD, I think this is fascinating in that right now, these patients are on long periods of maintenance with [lenalidomide] or high-risk patients are on bortezomib-lenalidomide. We have our own internal specialty pharmacy to manage the business of patients on lenalidomide long-term maintenance. It’s not always an easy drug for patients to take, and it’s very costly. So that maintenance phase can be very costly. More importantly, the patients would love to have a holiday and have something fixed duration—I see that now in CLL. Now, I think our doctors are starting to see the opportunity of fixed duration for first- and second-line treatment of CLL. I’d love to see it in multiple myeloma; I’d love to give patients a drug holiday. So hopefully that data will pan out, and we can have fixed-duration maintenance for multiple myeloma.