Moore Considers the Ide-Cel Subgroup Analyses and QOL in Myeloma

Patrick Moore, MD

Assistant Professor

Department of Internal Medicine

Rush University

Chicago, IL

Targeted Oncology: What was shown in the subgroup analysis of bridging therapy to idecabtagene vicleucel (ide-cel; Abecma) in relapsed/refractory multiple myeloma?

Patrick Moore, MD: [The investigators of KarMMa-3 (NCT03651128)] looked at the subgroup analysis of ide-cel after triple-class therapy and the change in disease burden by the bridging therapy received. So if patients received daratumumab [Darzalex]/pomalidomide [Pomalyst]/dexamethasone as bridging therapy prior to receiving CAR [chimeric antigen receptor] T-cell therapy, how was their response afterwards? Only about 20% of those patients had decreased disease. Then [60%] had no change in disease, and then [another 20% had] increased disease. In terms of decreased disease, it seems like most of the patients who responded the best were those who received carfilzomib [Kyprolis] and dexamethasone. I think that's also something you can notice; a lot of times with the patients, even pre-transplant, if they are slow responders or have progressive disease, I recommend patients being changed over to carfilzomib. From my personal experience, I have seen that they have a great response to carfilzomib compared with bortezomib [Velcade]. But we do use that as more in the second line, because it can cause more significant cytopenias.¹

Not as many people had decreased disease when it came to daratumumab/bortezomib/dexamethasone, which a lot of times is part of our first-line therapy as well. So it possibly could be related to patients having been exposed to this in the past. With the triplet therapy moving towards quadruplet therapy, and daratumumab being part of that new quadruplet, a lot of people are being exposed to daratumumab. Sometimes they don't necessarily respond as well compared with other regimens that they would not have seen before. Progression-free survival in these patients who had a decrease in their disease burden had a better progression-free survival [and] patients who did not have any change in their disease had better PFS compared with patients who had increased disease.

What were the responses and soluble B-cell maturation antigen (BCMA) by disease burden in the subgroup analysis results?

Soluble BCMA is measured in the blood [to see] how significant it is. Patients who had an increase in their disease typically had a higher amount of soluble BCMA in the blood, compared with patients who had no change in the disease or had a decrease in their soluble BCMA.

Looking at the different percentages of overall response, in the arm where there's an increased disease and then the arm with no change in disease and with decreased disease, the patients who have decrease in their disease pre-transplant with the bridging therapy were able to achieve a higher rate of stringent CR compared with patients who had an increase in disease. That goes to the fact that the higher the disease burden itself, the more likely these patients are going to not respond as well, and more likely that they're also going to relapse sooner than later. That speaks to the fact that the disease would be in these patients, likely more aggressive, [they] probably have higher-risk cytogenetics, etc.

What were the results for the patients’ quality of life (QOL) in the KarMMA-3 trial?

Investigators looked at how patients subjectively felt their life changed with ide-cel compared with patients who received standard of care.² In these patients, they checked...254 patients randomly assigned to the ide-cel arm, and 132 to the standard regimen.³ The baseline characteristics were balanced across the different treatment arms. Both arms had a median age of about 63 years, a median of 3 prior anti-myeloma regimens, and also a median time of myeloma diagnosis was about 4 years ago. Their QOL scores were generally comparable between the treatment arms. Basically, they're saying that patients had an improvement [with ide-cel].²

Patients are saying that they had an improvement in their fatigue when they received ide-cel compared with standard of care. There was a decrease in nausea, vomiting, pain, and dyspnea; less issues with insomnia, appetite loss, constipation, and diarrhea; and also subjectively, they felt like they had fewer financial difficulties in the ide-cel arm compared with standard of care. They felt like their disease symptoms were better in the ide-cel arm, subjectively compared with patients who were in the standard-of-care arm as well.

They also felt like their cognition was improved. A lot of times patients will complain about "chemo brain," the brain fog after they receive their therapies. So in that situation, they felt like they had better social functioning, cognitive functioning, emotional functioning, and physical ability in the ide-cel arm, compared with patients who receive the standard of care. This is at month 25; from the beginning of the trial to 25 months afterwards.

_References:

_{1. Einsele H, Rodriguez-Otero P, Arnulf B, et al. Idecabtagene vicleucel versus standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: KarMMa-3 subgroup analysis in patients receiving bridging therapy. Presented at: IMS 20th Annual Meeting and Exposition; September 27-30, 2023; Athens, Greece. Abstract P-008}

_{2. Delforge M, Patel KK, Eliason L, et al. Effects of idecabtagene vicleucel (ide-cel) versus standard regimens on health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma (RRMM) who had received 2–4 prior regimens: updated results from the phase 3 KarMMa-3 trial. Blood. 2023;142(1):96. doi:10.1182/blood-2023-179152}

_{3. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614}