Novel CAR T-Cell Therapy FCARH143 Delivers High Responses and Survival in Relapsed/Refractory Multiple Myeloma

FCARH143, an autologous B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy, demonstrated high response rates and survival in heavily pretreated relapsed/refractory (R/R) patients with multiple myeloma (MM). Findings from the phase 1 study (NCT03338972) achieved an overall response rate (ORR) of 100% among treated patients, with 64% achieving a stringent complete response.

At a median follow-up of 67.3 months, median progression-free survival (PFS) and overall survival (OS) were 15.5 and 32.1 months, respectively. These outcomes suggest that FCARH143 induces deep and durable remissions, even in patients with high disease burden or adverse cytogenetics.

Study Details

Employing a dose-escalation design, enrolled patients were stratified by bone marrow plasma cell involvement, from 10% to 30% or greater than 30%. All patients received lymphodepleting chemotherapy followed by FCARH143 infusion at doses ranging from 50 × 10⁶ to 450 × 10⁶ CAR-T cells. Three patients did not proceed to infusion because of disease progression or manufacturing delays.

Patients were eligible if they were 21 years of age or older, had an ECOG performance status 0, 1, or 2, and have relapsed or treatment-refractory disease with 10% or greater CD138-positive malignant plasma cells as determined by immunohistochemistry. Patients were excluded from enrollmentof they had a history of another primary malignancy that requires intervention beyond surveillance or that has not been in remission for at least 1 year, active hepatitis B or hepatitis C at the time of screening, or the presence of acute or chronic graft-versus-host disease.

The primary end point was safety, and secondary end points included ORR, duration of response, and PFS. The study’s intention-to-treat analysis, with a median follow-up of 69.6 months, revealed an ORR of 89.3% and a median OS of 30.2 months, underscoring the therapy’s efficacy across the broader enrolled population.

Patients in this trial were heavily pretreated, with a median of 8 prior lines of therapy, and 80% were triple-class refractory to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. Almost half (44%) had extramedullary disease, a known poor prognostic factor in multiple myeloma.

The median age was 64 years, reflecting a typical RRMM population with advanced disease and limited therapeutic options. Despite these high-risk features, FCARH143 elicited robust responses, suggesting its potential utility in patients with aggressive or refractory disease.

Safety

Safety outcomes were manageable, with cytokine release syndrome (CRS) occurring in 84% of treated patients, though only 8% experienced grade 3/4 events. Neurotoxicity was observed in 24% of patients, with 12% being grade 3 and no cases of grade 4/5.

No treatment-related deaths occurred, reinforcing the feasibility of FCARH143 administration in a real-world setting. These safety profiles align with those of other BCMA-targeted CAR T-cell therapies, though the absence of high-grade neurotoxicity is notable.

FCARH143 demonstrates potent and sustained antimyeloma activity with a favorable safety profile in patients with RRMM, regardless of disease burden or cytogenetic risk. The 100% response rate and prolonged survival in this heavily pretreated cohort highlight its potential as a transformative therapy. Further investigation in larger, randomized trials is warranted, particularly in high-risk subgroups.

REFERENCE:

Tuazon SA, Portuguese Aj, Pont MJ, et al. A phase 1 trial of fully human BCMA CAR-T therapy for relapsed/refractory multiple myeloma with 5-year follow-up. Blood. 2025;146(5):535–545. doi:10.1182/blood.2024027681