The Role of Transplant in the Era of Novel MM Therapies: Harsh Parmar, MD

Harsh Parmar, MD

While there is no cure for multiple myeloma, novel therapies are extending and saving lives, but they come at a price. Despite the promise of chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, stem cell transplantation remains the cornerstone treatment option for patients with multiple myeloma, explained Harsh Parmar, MD, associate professor of medicine, Hackensack University Medical Center.

For patients with relapsed/refractory multiple myeloma, CAR T-cell therapy and bispecifics are an important treatment option, but require strong communication with patients about the expenses to ensure the cost burden doesn’t impact treatment adherence and negatively affect long-term outcomes, he said.

This transcript has been lightly edited for clarity.

The American Journal of Managed Care® (AJMC®): How can we better assess and quantify the impact of financial toxicity on treatment adherence and long-term outcomes in patients with multiple myeloma who are receiving novel therapies such as CD38-targeted therapies?

Parmar: I think communicating with the patient is very important about these issues, because often physicians and other providers overlook this important aspect of rendering medical care. I think we need to implement some tools or instruments at regular intervals during treatment, which may [include] variables, such as out-of-pocket expenses, portion of income devoted to medical care, insurance claim denials, etc. These tools can be integrated into the EMRs [electronic medical records], so that physicians can accurately estimate the cost burden rendered on the patient, which is important, and such data will help us understand how much of an impact financial burden may have on treatment adherence and therefore long-term outcomes. Even when it comes to research, I believe it is equally important to design prospective studies which seek to answer such questions. Some of these therapies are lifesaving, and cost really should not become an issue.

AJMC: With the emergence of CAR T-cell therapies and bispecific antibodies, do you see the role of stem cell transplantation evolving in the treatment algorithm for multiple myeloma?

Parmar: I think for transplant-eligible patients, stem cell transplant still remains a cornerstone therapy [for] multiple myeloma, and this has been shown to have proven efficacy from data that spans many decades. There have been well-proven clinical trials on this particular question, and the emergence of CAR T and T-cell therapy has significantly increased the available options in the relapsed/refractory multiple myeloma setting. But to date, there have been no completed head-to-head clinical trials comparing transplant to CAR T or T-cell engager therapy in the front-line setting. There are many trials which are ongoing, seeking to address these questions, such as CARTITUDE-6 [NCT05257083]. But I believe rather than viewing 2 therapies as competing options, they should be viewed as therapies that complement each other.

As we know, myeloma continues to remain a cancer that we cannot cure, and keeping this in mind, overall survival, which represents the accumulation of all the progression-free survival that each therapy renders, relies on sequential administration of all these treatments, which includes transplant, CAR T, and bispecifics. All these therapies remain crucial, and they add to the survival of the patient; eliminating stem cell transplant in preference of CAR T or T-cell engager therapy reduces available effective therapies, and that would eventually compromise the survival trajectory. To answer your question, transplant should continue to hold its current place in the treatment algorithm of myeloma, despite the newer treatments that are coming up.

AJMC: You mentioned the transparent-eligible patient population specifically. What needs to be determined when trying to determine if someone is not eligible for stem cell transplant, and then what becomes the options?

Parmar: Obviously, patient preference is important. We discuss the risks [and] benefits associated with the transplant. At the end of the day, it's the patient's decision to choose which therapy is the most appropriate for them. But there are also other key factors which are considered, including the age of the patient, comorbidities that the patient may have, or other active second malignancies or infections that may need to be addressed before we can consider stem cell transplantation. If a patient is not a stem cell transplant candidate, then I think it's reasonable to pursue other therapies that we talked about, including CAR T therapy or T-cell engagers. Again, there are trials which are ongoing to address these questions, the impact of CAR T therapy in transplant-ineligible patients, such as the CARTITUDE-5 [NCT04923893] trial.

AJMC: In a situation where there are results from head-to-head trials, and CAR T-cell therapies and bispecifics start moving into the first line, how does that cost-effectiveness equation change at that point, given the large population size?

Parmar: You correctly pointed out that you have a significantly larger pool of patients when it comes to the newly diagnosed myeloma setting, as compared to the relapse/refractory setting. Obviously, the cost burden is going to increase significantly in such a setting. If myeloma was a disease that we were able to cure with CAR T therapy or T-cell engager therapy, then cost really should not be an issue. But we know that CAR Ts and T-cell engager therapies are not really curing the patient, which means if patients receive these treatments, and these treatments are very expensive—CAR T therapy can be as expensive as half a million dollars [and] some of the T-cell engager therapies are about the same; at least 1-year worth of T-cell engager therapy is about the same—then eventually, when they relapse, they will need subsequent treatments.

There is a concept in myeloma, which we call attrition, meaning we know that the pool of patient population declines with each relapse. Currently, as it stands, we are talking about CAR T therapy in the relapse setting, in the second line or perhaps the fourth line, we are looking at a smaller patient population pool. If we move these treatments up front, the cost burden is going to be significantly higher.

Yes, myeloma, in this day and age, is not a disease we are curing. Eventually, patients will relapse. We don't know that—the trials are ongoing—but I expect that they would eventually relapse, and when that happens, they will eventually need subsequent, sequential treatments. But obviously, the health care cost burden is going to increase.

AJMC: You mentioned relapse. What do we know about if somebody gets treated with a CAR T and they relapse. Can they get treated with another CAR T? What becomes the next treatment?

Parmar: As I was saying, we have data which has looked at CAR T therapy in the fourth-line setting, so patients have already exhausted most effective treatments in the earlier lines, and after relapsing following CAR T there are limited options. As we move these treatments in the earlier line, the data still needs to be explored. From my anecdotal experience, I can tell that patients who had CAR T in the earlier line when they eventually relapse and get subsequent therapies, as long as they've not been exposed to the effective treatments, those treatments still continue to work.

AJMC: Given the cost of CAR T and bispecifics, what have you seen in the way of innovative payment models or reimbursement strategies that might support these therapies in a sustainable way?

Parmar: I think CAR T therapy, in one way, can be considered cost-effective simply because it's one-and-done. You get the treatment one time, and then you come off therapy. This needs to be explored in the setting of T-cell engager therapy, where there is a lot of ongoing discussion about having clinical trials exploring limited-duration treatment. I think a lot of cost burden when it comes to myeloma is because of the indefinite nature of treatment that we offer to the patients. This is not just about T-cell engager therapy; even when it comes to monoclonal antibodies such as daratumumab or isatuximab, it's the same concept. You continue the treatment as long as it's working.

I think we need clinical trials that explore limited duration of therapy, and that will obviously have a significant impact once we recognize that limited or finite duration of therapy is sufficient to keep the patients in remission.