In the second article of a 2-part series, Joshua Richter, MD, discusses how the isatuximab, carfilzomib, and dexamethasone regimen fits into the landscape of treatment for patients with early relapsed multiple myeloma.
CASE SUMMARY
A 60-year-old White woman was diagnosed with stage III multiple myeloma.
Laboratory values:
Treatment
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: Based on the results of the IKEMA trial (NCT03275285), how does Isa-Kd compare with other therapies being investigated?
JOSHUA RICHTER, MD: When you look at time to next treatment [and all the other efficacy] metrics, Isa-Kd is going to outperform [previous regimens]. We see that median time to next treatment with Isa-Kd...which is the time from when the patient starts therapy to when you're going to change [their therapy again], is 44.9 months [95% CI, 31.6–not changed (NC)].1 Regardless of anything else, that's just an impressive number in the early relapse [setting]; it's hard to beat. Maybe the CARTITUDE-4 [NCT04181827] results will beat that, but the CARTITUDE-4 regimen is not approved and even when it's approved, it will be for a subset of patients.2 However, in trials [for CAR (chimeric antigen receptor) T-cell therapy]...they'll show you the [very high] response rates, but [not everyone on the trial] got the CAR T-cell therapy...for reasons including disease progression. So, they couldn't control the disease [long enough] and the patient died waiting for CAR T-cell therapy. Or they got immune suppression and an infection, and then they died.
I had a patient...who had 3 attempts at CAR T-cell collection, and they couldn't manufacture [the CAR T]. We have manufacture failures with this therapy still. So, CAR T-cell therapies are a great technology for a subset of patients, but it doesn't work for everyone. I'm all about utility. I'm all about [focusing on] the patient that you see in the clinic tomorrow, that walks in with their laboratory results now showing their creatin is rising. This is someone where we can't wait. So, an anti-CD38 monoclonal antibody plus carfilzomib is our go to, but I would argue that Isa-Kd has the best outcomes [for these patients] so far.
What were the long-term results for patients with 1q21 in their disease?
To me, the...[main efficacy marker to look at in this subgroup] is median progression-free survival [PFS], because you need to be able to tell your patient if it's going to work or not. For the most part, with either regimen the response rates are all high, so it's got to work, but the question I always think about in the back of my head is, but for how long [will it work]? For that reason, PFS is the efficacy result we focus on. In patients with standard risk [on the IKEMA study], the median PFS was 20.3 months [range, 15.2-28.2] with Kd vs 42.4 months [range, 26.3-NC] with Isa-Kd.3 So even for the patients with standard risk, it improves their survival. It's not just for those [with a higher risk or abnormality].
In patients with a 1q21 addition, the median PFS was 16.2 months [range, 10.2-24.8] in the Kd arm vs 25.8 months [range, 17.1-38.2] in the Isa-Kd arm. For patients with isolated 1q21, it was 16.2 months [range, 10.2-25.1] in the Kd arm vs 38.2 months [range, 18.8-NC] in the Isa-Kd arm. [For those patients who gained] 1q21, the median PFS was 18 months [range, 10.2-25.0] with Kd alone vs 30.2 months [range, 20.8-NC] with Isa-Kd. The result that...[I think] shows how bad amplification of 1q21 is…that the median PFS is 14.5 months [range, 2.8-NC] with Kd vs 18.4 months [range, 13.1-NC] with Isa-Kd. That to me is a huge difference [from the other 1q21 groups]. If the patient had 3 copies and I put them on Isa-KD, they’re in remission for an average of 30 months, but if they had 1 extra copy of 1q21 you almost half that [PFS] to 18 months.
References:
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