In the second article of a 2-part series, Douglas Sborov, MD, discusses the toxicities seen with isatuximab and how this therapy can impact patients in rural areas relying on community center treatment.
A 60-year-old White woman was diagnosed with stage III multiple myeloma.
Two years on lenalidomide maintenance
The patient was then started on isatuximab (Sarclisa), carfilzomib (Kyprolis), and dexamethasone (Isa-Kd) and achieved a very good partial response (VGPR).
Targeted Oncology: What were the toxicities seen with Isa-KD in patients with multiple myeloma?
DOUGLAS SBOROV, MD: The important thing to highlight is that the majority of treatment-emergent adverse events [TEAEs] were driven by the Isa-KD arm, not so much isatuximab [by itself].1 I think that isatuximab is well tolerated and is as well tolerated daratumumab [Darzalex], but [there is a] difference between infusion and injection [methods for these therapies]. Both drugs are associated with infusion reactions in weeks 1 and 2 of cycle 1, but once you get into those first couple weeks [of treatment], that goes away.1
However, it is a big deal because daratumumab is given weekly for 2 months, then given every other week for 4 months thereafter, whereas isatuximab is given weekly for the first cycle [of therapy] then given every other week indefinitely. After that 6-month mark, patients are ultimately getting less [of the drug compared with] when they're getting the daratumumab. [The drug manufacturer] is working hard to try to figure out if there's a better dosing frequency [that can] match up better with the daratumumab, but that has not yet been reached.
How does the addition of isatuximab compare with other therapy considerations at this point in treatment?
The addition of isatuximab did not increase the rate of cardiac events.1 I think that's an important point to highlight, but in my opinion, we often don't see any significant toxicity with the CD30 antibodies other than infections, and sometimes some gastrointestinal TEAEs. I would argue that [when looking at both] the CANDOR [NCT03158688] and IKEMA [NCT03275285] studies...I would say that the majority of patients will not be continued on daratumumab until disease progression.
The majority of patients who are going through to first-line of therapy will probably be on immunomodulatory drugs indefinitely. They'll probably get daratumumab, but that will be a for time limited duration, maybe 1 to 3 years long. But the progression-free survival is so long right now,2 that I don't think we need to be continuing these patients, unless they have extremely high-risk disease—then we need to be [moving faster]. I think that most of us are thinking about…[using it as much as we can], but let's not burn the patient out.
Are there any other advantages to this drug outside of efficacy data?
If you have home health [for a patient in a rural area] then you can send them a body device [to track their vitals] and if they have a home health nurse, they can then give the patient isatuximab at home.... All of a sudden, you have a regimen that you're doing at home [for the patient in the middle of a rural area].... There may be some interesting approaches [with isatuximab], and I think one of the things that I've talked to the [drug manufacturer] about is that [at our practice], we have this unique patient population out in the middle of nowhere, and [we need to ask]: how do we improve the delivery of care to those folks? This may be one of those ways, but [they still need time to develop].
1. Martin T, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. Blood Cancer J. 2023;13(1):72. doi:10.1038/s41408-023-00797-8
2. Usmani SZ, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022;23(1):65-76. doi:10.1016/S1470-2045(21)00579-9