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IMW 2021 | Updates on ide-cel and cilta-cel for myeloma

Saad Usmani, MD, MBBS, MBA, of Levine Cancer Institute/Carolinas HealthCare System, Charlotte, NC, gives an overview of the latest updates on the use of chimeric antigen receptor T-cell (CAR-T) therapies for multiple myeloma, highlighting the approval of idecabtagene vicleucel (ide-cel) based on the findings of the Phase II KarMMa trial (NCT03361748) and recent data on ciltacabtagene autoleucel (cilta-cel). Dr Usmani comments on high response rates observed in relapsed/refractory patients receiving either of these therapies, and discusses the need to further understand resistance mechanisms and to optimize the duration of CAR-T therapy using measurable residual disease (MRD) assesment. This interview took place during the 18th International Myeloma Workshop (IMW 2021) congress.

Transcript (edited for clarity)

Ide-cel, which used to be called BB2121, was ahead in terms of its clinical development with the KarMMA studies, the original Phase I dose-escalation trial, as well as the Phase II study. And it was the first cellular therapy that just got its FDA approval this year and then also its approval by EU and in Canada and Switzerland, if I remember correctly. And now, cilta-cel is coming down the pike...

Ide-cel, which used to be called BB2121, was ahead in terms of its clinical development with the KarMMA studies, the original Phase I dose-escalation trial, as well as the Phase II study. And it was the first cellular therapy that just got its FDA approval this year and then also its approval by EU and in Canada and Switzerland, if I remember correctly. And now, cilta-cel is coming down the pike. These are different constructs, the populations, even though there might be five or six median prior lines of patients and triple-class refractory. Even within that subgroup of patients, you can’t compare one study versus the other, but both are quite active. I think in KarMMA, in the higher dose group of 450 million CAR + T-cells being given to patients per kilogram body with overall response rate is over 80%.

With cilta-cel it’s a different construct. It has two BCMA binding domains. The cell dose is small and that allows for a delayed expansion, but overall response rates are very impressive at about 98% and a CR rate of over 80% with an 18 month follow-up. So, I think what both of these CAR-Ts are very promising. There are clinical trials looking at earlier lines of treatment.

What we really need to learn from this experience is if patients are losing their response after CAR T-cell therapy, is it being driven by disease biology or is it because of the immune repertoire or the bone marrow microenvironment? So, understanding the resistance mechanisms is going to be important. I do feel that the CAR-Ts will move into the earlier lines of setting and we are going to be defining duration of treatment based on sustainability of MRD-negativity. And this is where the one and done kind of approach with CAR-Ts will come in handy.

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Disclosures

Saad Usmani, MD, MBBS, MBA, has received research funding from Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, Takeda; has received consulting fees from Abbvie, Amgen, BMS, Celgene, GSK, Genentech/Roche, Janssen, Karyopharm, Merck, Oncopeptides, Sanofi, Seattle Genetics, SkylineDx, Takeda; and has received speaking fees from Celgene, Janssen, Sanofi, Takeda.