Kiavasch Mohammad Nejad Farid, MD, of Heidelberg University Hospital.

Kiavasch Mohammad Nejad Farid, MD, discusses 2 planned investigations of MDC-CAR-BCMA001 in relapsed/refractory multiple myeloma and AL amyloidosis.

"We are looking forward to the ongoing [phase 1] CARLOTTA001 trial [being conducted] by our colleagues from Dresden, Germany. 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 in the second line of treatment."

Kiavasch Mohammad Nejad Farid, MD, of Heidelberg University Hospital, discusses next steps for evaluating the novel second-generation BCMA-directed CAR T-cell construct MDC-CAR-BCMA001 in patients with relapsed/refractory multiple myeloma and systemic light chain (AL) amyloidosis.

Findings from a study investigating compassionate use of the in-house–manufactured BCMA-targeted CAR T-cell construct MDC-CAR-BCMA001 in patients with BCMA-pretreated,triple-class–refractory multiple myeloma and AL amyloidosis were presented at the 

. Data demonstrated clinical activity of MDC-CAR-BCMA001 among heavily pretreated patients in the overall study population, including those with limited treatment options due to AL amyloidosis, a setting where CAR T-cell therapy is not yet approved.

These preliminary findings support the ongoing phase 1 CARLOTTA001 trial (NCT05836896), led by investigators in Dresden, Germany, Farid detailed. CARLOTTA001 is currently enrolling patients aged 18 years or older with relapsed/refractory diffuse large B-cell lymphoma or multiple myeloma. Eligible patients must have an ECOG performance status of 0 to 2 and adequate organ function. Upon enrollment, patients will receive lymphodepleting conditioning chemotherapy followed by a single intravenous infusion of MDC-CAR-BCMA001 administered at 1 of 4 dose levels in an ascending dose-escalation design. Primary end points of the study include identification of the maximum tolerated dose (MTD) and safety.

To further define the feasibility and therapeutic activity of MDC-CAR-BCMA001 in AL amyloidosis, particularly in the second-line setting, the phase 1 CLEAR-AL trial is being initiated, Farid continued. This study aims to expand upon the compassionate-use data and provide insight into the potential role of BCMA-directed CAR T-cell therapy in patients with this rare plasma cell disorder. Collectively, these trials may help delineate the future integration of CAR T-cell therapy in the management of AL amyloidosis and relapsed/refractory plasma cell malignancies.

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

Videos

Dr Farid on Current and Future Investigations of MDC-CAR-BCMA001 in Myeloma and AL Amyloidosis

Dr Farid on the Efficacy of MDC-CAR-BCMA001 in R/R Myeloma and AL Amyloidosis

"BCMA has emerged as a very attractive target for immunotherapies. CAR T-cell therapies are not always an option, especially for patients with AL amyloidosis, where [these agents] are not currently approved. To address this gap, we pursued the compassionate use of our in-house manufactured CAR T-cell construct."

Kiavasch Mohammad Nejad Farid, MD, Heidelberg University Hospital, discusses the rationale for evaluating the novel second-generation BCMA-directed CAR T-cell construct MDC-CAR-BCMA001 for patients with relapsed/refractory multiple myeloma and systemic light chain (AL) amyloidosis in the compassionate-use setting.

Although BCMA is a well-established immunotherapeutic target in multiple myeloma, CAR T-cell therapy remains unavailable for AL amyloidosis, where treatment options are particularly limited and disease biology poses unique challenges, Farid began. Furthermore, BCMA-directed CAR T-cell therapy is not feasible for certain patients, particularly those with relapsed/refractory multiple myeloma who previously progressed on a BCMA-targeted agent, he explained. To potentially address these challenges and unmet needs, investigators implemented compassionate use of the in-house–manufactured BCMA-targeted CAR T-cell construct MDC-CAR-BCMA001 in patients with BCMA-pretreated triple-class refractory multiple myeloma and AL amyloidosis, Farid detailed.

Findings from this study were presented at the 

 and showed clinical activity with MDC-CAR-BCMA001 among heavily pretreated patients in the overall study population. Of the 6 patients who received MDC-CAR-BCMA001, 5 achieved a hematologic response. Four of these responders achieved a complete response (CR), and 1 patient experienced a very good partial response (VGPR). Moreover, all patients with CR achieved minimal residual disease negativity. The median decrease in free light chains was 98.4%, underscoring the depth of hematologic response. The median time to initial response was 14 days, and the median time to best response was 41 days. Organ responses were also observed in this cohort. One patient each achieved a cardiac VGPR, a renal VGPR, and improvement in polyneuropathy.

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

Kiavasch Mohammad Nejad Farid, MD, discusses how compassionate use of MDC-CAR-BCMA001 could address unmet needs for multiple myeloma and AL amyloidosis.
 

Dr Farid on the Rationale for Evaluating MDC-CAR-BCMA001 in R/R Myeloma and AL Amyloidosis

“[Among] these 6 patients with challenging baseline [characteristics], we achieved exceedingly good efficacy with 5 patients responding, 4 achieving a complete response [CR], and all patients who achieved a CR also became minimal residual disease negative.”

Kiavasch Mohammad Nejad Farid, MD, Heidelberg University Hospital, discusses the efficacy findings from a study of the novel second-generation BCMA-directed CAR T-cell construct MDC-CAR-BCMA001 in relapsed/refractory multiple myeloma and systemic light chain (AL) amyloidosis. 

, Farid presented data from a study that showed that at a median follow-up of 13 months, 5 of the patients who received MDC-CAR-BCMA001 (n = 6) achieved a response. Four of these responders achieved a complete response (CR) and all patients who experienced a CR achieved minimal residual disease negativity, Farid said. All responders remained alive at the median follow-up, with 4 remaining in sustained remission without the need for additional therapy, he added. In patients with AL amyloidosis, achieving rapid and deep hematologic response is crucial, he said.

Additional data from the study demonstrated that the median decrease in free light chains was 98.4%. The median time to response was 14 days, and the median time to best response was 41 days. In terms of organ responses, 1 patient each achieved a cardiac very good partial response (VGPR), a renal VGPR, and an improvement in polyneuropathy.

In terms of safety, grade 1 and 2 cytokine release syndrome was reported in 50% and 33% of patients, respectively. One patient experienced grade 3 or higher CRS. The median time to CRS onset was 1 day (range, < 1 to 3), and the median duration of CRS was 4 days (range, 2-6). Sixty-seven percent of patients received tocilizumab (Actemra) and 33% were treated with corticosteroids. Immune effector cell-associated neurotoxicity syndrome and other late neurtoxicities were not reported. Sixty percent of patients experienced grade 1 early immune effector cell-associated hematotoxicity (ICAHT); 20% had grade 2 ICAHT and received granulocyte colony-stimulating factor. Grade 1 ICAHT was reported in 17% of patients and resolved spontaneously.

Kiavasch Mohammad Nejad Farid, MD, discusses the efficacy of MDC-CAR-BCMA001 in relapsed/refractory multiple myeloma and systemic light chain (AL) amyloidosis. 

Kiavasch Mohammad Nejad Farid, MD

Articles

Dr Farid on Current and Future Investigations of MDC-CAR-BCMA001 in Myeloma and AL Amyloidosis

Dr Farid on the Rationale for Evaluating MDC-CAR-BCMA001 in R/R Myeloma and AL Amyloidosis

Dr Farid on the Efficacy of MDC-CAR-BCMA001 in R/R Myeloma and AL Amyloidosis