EHA 2025 | The current role of CAR T-cell therapy in myeloma and how it is shaping the treatment landscape

CAR T-cell therapy is a revolutionary therapy for multiple myeloma. Most certainly the landscape is changing. Originally CAR T-cell therapies were approved in late lines and heavily pre-treated relapsed/refractory myeloma. Now we have KarMMa-3 and CARTITUDE-4, essentially looking at patients being treated in earlier lines and compared to standard of care options. And now we do have approvals of CAR T-cell therapy in earlier lines. So we have ciltacabtagene autoleucel as early as second line of therapy in patients who are PI and IMiD exposed and lenalidomide refractory. And then as soon as third line, we have approvals both in the USA and in the EU of idecabtagene vicleucel in third line and beyond for patients who are triple class exposed to an IMiD, PI and CD38. 

So generally speaking, we also have other clinical trials looking at CAR-T in the relapsed setting with different targets beyond BCMA and BCMA like anito-cel is coming down the pipeline. The data will be presented later this afternoon with longer follow-up from what we’ve seen so far. You know the outcomes look great, you see deepening of those CR and stringent CRs and there are no evidence of non-ICANS neurotoxicities or colitis, which is exciting. 

But we also have ongoing clinical trials in the frontline setting right – we have CARTITUDE-5 we have CARTITUDE-6 and you know that might answer the question of transplant versus CAR-T in the frontline setting. And then different targets as I talked about, including arlocabtagene autoleucel, which is a GPRC5D-targeted CAR-T which is also showing very excellent results/ even in the prior BCMA-exposed patients. And we have other dual-targeted CARs such as Fast-CAR, CD19/BCMA and BCMA/GPRC5D and certainly preliminary outcomes look good but we would need to look at safety and durability of response with those products. 

From a barrier standpoint I mean there are multiple considerations here. Manufacturing has significantly improved in terms of duration of manufacturing, scalability of manufacturing. We do have novel prognostic models, some to be presented at IMS, looking at what are the high risk factors for patients. We are doing more outpatient CAR-T to help maximize resources such as hospital beds. And we are identifying prophylaxis strategies, as well as patients who might be at increased risk of some of these non-ICANS toxicities and prophylaxis strategies by looking at CAR-T expansion and maximum ALC expansion between day 10 to 14 and different anti-inflammatory type of approaches. Certainly we have work to do. Manufacturing is improving. You know, there’s work in the in vivo CAR-T space as well. But the field looks exciting. 

I guess I really would like to conclude by stating some CARTITUDE-1, right? The five-year data looks extremely exciting. We see with the five-year follow-up, 97 patients were infused. Of them, a third or 33% were alive and without evidence of disease progression. Truly impressive. If we think about the magnitude of these results, I mean, it’s transformative treatment with potential curative benefit for multiple myeloma or functional cure, which is a very exciting time for us and for our patients.

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