CAR-T Meeting 2026 | An update on MDC-CAR-BCMA001, a novel anti-BCMA CAR T-cell construct, in R/R systemic AL amyloidosis

So I’m glad to be back on VJHemOnc to talk about a topic that I’m very passionate about, so CAR T-cell treatment in AL amyloidosis. And last year, I have presented data on a mixed cohort of myeloma and three AL amyloidosis patients, and now we were able to expand our cohort to seven AL amyloidosis patients, and I will provide an update on this cohort and also present our new trial project. 

So just a quick summary. MDC-CAR-BCMA001 is a BCMA-targeting CAR T-cell construct. We treated our patients with a fixed dose of 800 million CAR T-cell cells after lymphodepleting chemotherapy. And just to make it short, nothing but continued success with this construct. Fortunately, we had a great overall response in these heavily pretreated patients with a median prior line of five therapies. And six out of seven patients responded, three of them achieving a complete response, three achieving a very good partial response. And all patients that achieved a complete response also became MRD negative. We also saw impressive organ responses. And what’s very striking is that it works so quickly – median time to best response is 13 days only, which is so important for these patients to enable organ recovery. 

And when talking about CAR T-cell therapy, toxicity is always a concern, especially when treating this very vulnerable patient cohort. And therefore, we had to establish really a strategy that’s tailored to these pre-existing organ insufficiencies of this cohort. And this strategy includes the use of fludarabine-free lymphodepleting regimens in selected cases with severe amyloid-related neuropathy or nephropathy, and the earlier than usual use of tocilizumab to already mitigate prolonged grade 1 CRS. For example, you know, persistent tachycardia or high fevers can be very problematic for patients with cardiac involvement and also the very restrictive use of corticosteroids, which can cause severe fluid imbalances in these patients. And by implementing this strategy, we were able to manage CRS very well. We had no irreversible toxicities, we had no neurotoxicity at all, and that’s obviously something that wasn’t expected in this way, but we were very fortunate to see these results for these patients who otherwise wouldn’t have any other promising or approved treatment options. 

And when treating AL amyloidosis, the clones that are targeted, the plasma cell clones, are usually very small compared to the disease state of myeloma. And what’s special about MDC-CAR-BCMA001 is that it has very high avidity and great expansion kinetics, which makes it very suitable for targeting these small clones compared to myeloma. And we hope to be able to expand our field of application to other gammopathies of clinical significance that also have a very small clone size. 

And last but not least, I would like to present the concept of our prospective clinical trial, IIT, phase one trial called CLEAR-AL or clear all – you can decide. And it’s already approved by the European authorities and will start already next month in March, 2026. Very exciting. And this trial will prospectively investigate the feasibility of BCMA-directed CAR T-cells, so MDC-CAR-BCMA001, in relapsed/refractory AL amyloidosis patients as early as in second line of treatment. And what’s part of the inclusion criteria? We will include patients with cardiac involvement up to stage 3A, according to the European modification of the Mayo staging system. We will include patients who had a suboptimal response to first-line treatment with the gold standard as Dara-CyBorD as early as after two cycles if response is inadequate, so very, very early deepening of response or the chance to deepen the response, and we will exclude patients with cytogenetic evidence of translocation (11;14), which will sensitize the disease towards BCL2 inhibition. And what’s really noteworthy about this trial is that we will also include patients who formally achieve an adequate hematologic response, for example, a VGPR, but who fail to achieve any kind of organ response or even show signs of organ progression, presumably due to continued clone activity. And that really mandates deepening of hematologic response. And we hope to be able to use MDC-CAR-BCMA001 to achieve these profound responses that are needed, and perhaps maybe to really eradicate these small but very dangerous clones.

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