How BCMA CAR T-Cell Therapy Provides Later-Line Options in R/R Multiple Myeloma

Targeted Oncology: What has been the response to idecabtagene vicleucel (ide-cel; Abecma) for patients with multiple myeloma on a bridging therapy prior to this treatment?

ABDULLAH KHAN, MBBS: There have been subset analyses [of the phase 3 KarMMa-3 study (NCT03651128) data] of what happens when the patient gets bridging therapy then gets their chimeric antigen receptor [CAR] T-cell therapy.¹ [Investigators wanted to see if] patients responded or didn’t respond during bridging therapy, and [what they saw was their disease burden grew while bridging to CAR T-cell therapy, in some cases]…. Physicians have also looked at maintenance therapy and other strategies after CAR T-cell therapy to help it work even better, but for now, it's just 1 dose [of ide-cel that’s] given.¹ But when was the last time we can recall patients with multiple myeloma being away from the clinic for a year [without needing additional] therapy? It's changing the [treatment] algorithm.

Abdullah Khan, MBBS​

Assistant professor, Division of Hematology

The Ohio State University

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What adverse events (AEs) associated with ide-cel should be noted?

The most important AE to highlight was that 88% [of patients experienced] cytokine release syndrome [CRS] at any grade, but 4% [had grade 3 or 4 CRS, and there were 2 deaths]...on the study overall.2 Any-grade neurotoxic events were seen in 15%, while high-grade neurotoxic events were seen in 3%.² It's not the perfect therapy, but these are now becoming more manageable toxicities as we're becoming more aggressive with prophylaxis [treatment]…alongside debulking the patient’s disease as much as we can prior to the therapy.

We're finding ways to make this treatment better [and more tolerable]. I think we also have a better understanding of how to support them from an infection perspective. Sometimes, we run into issues with cytopenia, and their white blood cell count might measure low, but in my experience, they come back up after a period of time. For example, there are some patients we’ve had to rescue with their stored stem cells to bring up their platelet counts, but these are all the things we're learning to improve outcomes with CAR T-cell therapy.

How has ide-cel performed in the real-world setting?

[Looking at] quality-of-life data, many recorded negative symptoms decreased while all positive measurements got even better.³ They've even done real world analyses of outcomes with ide-cel. This is…[focused on] the later line data after the fourth-line therapy, and the CRS rates in the clinic are similar between the trials, [along with] neurotoxic events.⁴ The trial patients did do better compared with what we see in the clinic, and that might [have to do with] opening the floodgates [in the real-world setting].

Patients [in the real-world setting are] on, for example, their tenth line of therapy and they're not going to do as well as [the patient on] their fourth line of therapy. If they've had a prior B-cell maturation antigen therapy, like belantamab mafodotin [Blenrep], in the clinic and then you send for CAR T-cell therapy, will they respond to it? Yes, they will; it's not as great as a response at [approximately] 71%, but those are still pretty good odds of responding to the BCMA CAR T-cell therapy.⁴ Depending on the type of prior BCMA therapy there's also differences [in outcomes], but I think if you have a patient who's gotten something like teclistamab-cqyv [Tecvayli] and then you're thinking [about what you would] still use down the line, CAR T-cell therapy is not an unreasonable option.

REFERENCES:

1. Einsele H, Rodriguez-Otero P, Arnulf B, et al. Idecabtagene vicleucel (ide-cel) versus standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: KarMMa-3 subgroup analysis in patients receiving bridging therapy. Presented at: 2023 International Myeloma Society Annual Meeting; September 27-30, 2023; Athens, Greece. Abstract P-0008

2. 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

3. Delforge M, Patel K, 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(suppl 1):96. doi:10.1182/blood-2023-179152

4. Sidana S, Ahmed N, Akhtar OS, et al. Real world outcomes with idecabtagene vicleucel (Ide-Cel) CAR-T cell therapy for relapsed/refractory multiple myeloma. Blood. 2023;142(suppl 1):1027. doi:10.1182/blood-2023-181762