Multiple Myeloma - Episode 1
Rebecca Nelson, PharmD, BCOP, is the malignant hematology clinical pharmacy supervisor, Moffitt Cancer Center.
Patient fitness, prior treatments, and cardiovascular effects are all considerations in treatment decisions in multiple myeloma, according to Rebecca Nelson, PharmD, BCOP. Nelson, the malignant hematology clinical pharmacy supervisor at Moffitt Cancer Center, discussed pharmacy considerations with The American Journal of Managed Care®. This interview has been lightly edited for clarity and length.
Despite advances in treatment of multiple myeloma, almost all patients will eventually relapse. How do you define relapsed or refractory multiple myeloma?
Relapsed/refractory is typically defined as any [disease that is] nonresponsive or progressive on therapy, or within 60 days of the last treatment in patients who have actually achieved a minimal response or better on prior therapy. This is typically based on the IMWG [International Myeloma Working Group] consensus guidelines, and those guidelines do say that the [definition is] recurrence of disease after prior response on the basis of objective laboratory or radiological criteria. These criteria could be greater than or equal to 25% of the increase of monoclonal protein in the serum or the urine, or it could be greater than 25% difference between the involved and uninvolved serum free light chains. Other options would be that it would be the increase of 10% of the absolute percentage of bone marrow plasma cells, or even the development of new plasmacytomas or hypercalcemia.
What patient-specific factors influence the choice of therapy in relapsed/refractory multiple myeloma?
Ultimately, these would be fit vs frailty; the availability of any of the clinical trials that the patient might be eligible for; other things that we do look at for the center would be renal function, their liver function, the aggressiveness of their relapse. Also, [we look] at the patient’s goals, so we look at IV [intravenous] treatments vs PO, or oral, treatments. Does the patient have transportation to the infusion center? Are they able to take their pills? What about the overall tolerance that they’ve had with prior therapies? That’s something else that we look at. Does the patient currently have peripheral neuropathy? We know a lot of multiple myeloma treatments do cause peripheral neuropathy, so it’s definitely something that we would look at.
Also, we look at cardiovascular effects. We know many treatments for our patients have some cardiovascular toxicity; maybe the patient had a previous MI [myocardial infarction]. Do they have heart failure? All of those things would be factors that we would certainly consider prior to starting any treatments.
Ultimately, the goals of care are what we keep in mind, so in discussing [options] with the patient, we exhaust those PO or oral options prior to starting any IV, especially since a lot of those treatments have oral and IV as combinations, and those might actually be better treatments for the patients. But we would ultimately just be discussing this with them. This could be due to working full time or the liability of transportation to the center, because that’s often something that we do see with many of our patients.
In your experience, which treatment regimens are the most frequently utilized today in relapsed/refractory multiple myeloma?
I think this would ultimately depend on the induction regimen that was used. If the patient did not have any anti-CD38 antibody upfront, then we would utilize DPD, or dara-pom-dex [daratumumab plus pomalidomide and dexamethasone]. If they were unable to tolerate an IMiD [immunomodulatory imide drug], then we will use [daratumumab, carfilzomib, and dexamethasone]. If they present a relapse with the plasmacytomas then we would often use [carfilzomib-cyclophosphamide-dexamethasone], typically.
We generally are not using antibody-drug conjugates due to the BCMA [B-cell maturation antigen] targets and the potential that these patients actually may start CAR [chimeric antigen receptor] T[-cell] treatments. So ultimately, we keep the patient goals in mind and certainly look at those side effect profiles specifically to the treatment options that we’re presenting to the patient.
How does the total cost of care vary with the fixed dosing and variable dosing in anti-CD38 regimens, and are there particular patients who may benefit from the use of one agent vs another?
This is a fantastic question. I actually think that until we have a pharmacoeconomic analysis that really looks at this, it’s really hard to have a definitive comment. I do think that an overall thing to consider when looking at total cost of care of the options is what are the IV charges, so looking at contracting for the center’s site of care, funding combination treatments—a lot of these agents are given with combinations, so what is that cost—and then looking at overall ADR management with the different options out there….There are a lot of different factors that come into total cost of care, so until we have analysis that looks at that, it’d be hard to say which one is actually better than the other.
Can you provide any closing thoughts on the pharmacy considerations for multiple myeloma that you find noteworthy?
I think overall, especially with multiple myeloma—because I do have experience in all the hematologic malignancies—there is a growing number of therapies, especially combination regimens, and so it’s really important to stay informed about these combinations and educate not only our patients, but also our staff. A lot of these combination therapies are coming out and these papers actually are coming out prior to them being put into these clinical consensus guidelines like NCCN [National Comprehensive Cancer Network]. So, it is important to keep abreast of these new articles that are coming out. If we have access to those, those actually will be beneficial to getting reimbursement and educating our patients but also reimbursement for these treatments for the patients, payers, and the institution.