Responses With Compassionate Use of MDC-CAR-BCMA001 Support Further Study in R/R Myeloma and AL Amyloidosis

Kiavasch Mohammad Nejad Farid, MD

Given the absence of commercially available BCMA-directed CAR T-cell therapies for systemic light chain (AL) amyloidosis and diminishing therapeutic outcomes observed across successive lines in BCMA-pretreated multiple myeloma, the deep and durable responses observed with compassionate use of MDC-CAR-BCMA001 among heavily pretreated patients suggest that this investigational agent could address a significant unmet need, according to Kiavasch Mohammad Nejad Farid, MD.

In an interview with OncLive®, Farid expanded on results from a study investigating this novel, second-generation BCMA-targeted CAR T-cell construct, which were presented during the 51st Annual EBMT Meeting. At a median follow-up of 13 months, overall responses were achieved by 5 of the 6 patients who received MDC-CAR-BCMA001, including 4 complete responses (CR) and 1 very good partial response (VGPR). Furthermore, all patients who achieved a CR also attained minimal residual disease negativity (MRD). The 12-month overall survival rate was 83%, and the 12-month event-free survival rate was 50%. Four patients had sustained remission without requiring additional therapy. Three patients also experienced organ responses, including 1 cardiac VGPR, 1 renal VGPR, and 1 improvement in polyneuropathy.

“[For patients with] AL amyloidosis in particular, it’s crucial to achieve deep and rapid hematologic responses,” Farid stated. “We observed near-total suppression of amyloidogenic serum free light chains [with MDC-CAR-BCMA001], which [translated] into impressive organ responses.”

Farid, who is a medical oncologist in the Department of Internal Medicine V, Hematology, Oncology and Rheumatology, at Heidelberg University Hospital in Germany, also highlighted the tolerability of this novel MDC-CAR-BCMA001 CAR T-cell therapy in AL amyloidosis and noted avenues for further investigation of this agent in other hematologic malignancies and/or earlier treatment lines.

OncLive: What was the rationale for evaluating the compassionate use of MDC-CAR-BCMA001 for patients with relapsed/refractory multiple myeloma and AL amyloidosis?

Farid:I’m excited to share our experience with this novel BCMA-targeting CAR T-cell construct, which we have already successfully used in heavily pretreated patients with AL amyloidosis and multiple myeloma. BCMA has emerged as an attractive target for immunotherapies. However, CAR T-cell therapies are not always an option, especially for patients with AL amyloidosis, where they are not currently approved. To address this gap, we pursued the compassionate use of our in-house–manufactured CAR T-cell construct.

What is unique about the mechanism of action of MDC-CAR-BCMA001 compared with other CAR T-cell constructs?

It’s noteworthy that we are using a special and novel CAR T-cell construct. [MDC-CAR-BCMA001 is] a second-generation CAR [T-cell product] that targets BCMA—similar to ciltacabtagene autoleucel [Carvykti; cilta-cel] and idecabtagene vicleucel [Abecma; ide-cel]—but there are some key differences. [This construct] uses a CD28 co-stimulatory domain and has uniquely high avidity, which allows for its use in low antigen-expressing disease.

How was this investigation of MDC-CAR-BCMA001 conducted?

We treated 6 consecutive patients on a compassionate-use basis with a fixed dose of 800 million CAR T cells following lymphodepleting chemotherapy with fludarabine and cyclophosphamide or bendamustine. [Of these patients], 3 had multiple myeloma, 2 had AL amyloidosis, [and 1 had concurrent multiple myeloma and AL amyloidosis]. [Patients in this trial] were heavily pretreated, had severe vital organ dysfunction, and had triple-refractory disease, which made their baseline [characteristics] challenging [to factor into treatment decisions].

What did this study reveal about the initial activity of MDC-CAR-BCMA001 in the compassionate-use setting?

[Among] these 6 patients with challenging baseline [characteristics], we achieved exceedingly good efficacy, with 5 patients responding, 4 achieving a CR, and all patients who achieved a CR becoming MRD negative—which is striking efficacy in this patient population. All responders are alive after a median follow-up of 13 months, and 4 of them remain in sustained remission without needing further therapy.

What should be known about the agent’s safety profile?

Fortunately, and most importantly, the therapy was well tolerated. There were many concerns about toxicity, [including] how the [patients with] AL amyloidosis would tolerate [cytokine release syndrome (CRS)], but we [saw] mainly low-grade CRS and no neurotoxicity at all. By optimizing supportive care, including earlier-than-usual use of [tocilizumab (Actemra)] and restrictive use of [corticosteroids], we could manage CRS without irreversible toxicities. Cytopenias and [hypogammaglobulinemia] were expected adverse effects, but infections were mostly low-grade and manageable overall.

What next steps are planned to further elucidate the agent’s suitability for the treatment of patients with AL amyloidosis, multiple myeloma, and other hematologic malignancies?

We are looking forward to the ongoing [phase 1] CARLOTTA001 trial [(NCT05836896) being conducted] by our colleagues from Dresden, Germany. [This study] is currently enrolling patients with relapsed/refractory [diffuse large B-cell lymphoma] and [multiple myeloma] to [receive] this same CAR T-cell construct. We are also going to launch a phase 1 trial called CLEAR-AL [which will evaluate the use of MDC-CAR-BCMA001 in patients with] relapsed/refractory AL amyloidosis as early as the second line of treatment.

Disclosures: Farid reported receiving travel grants from Pierre Fabre and Kite/Gilead.

Reference

Farid K, Hegenbart U, Schönland S, et al. Successful treatment of patients with heavily pretreated systemic light chain al amyloidosis and multiple myeloma with the novel MDC-CAR-BCMA001. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025. Florence, Italy. Abstract OS14-06.