Efficacy and safety of a fully human BCMA CAR T-cell therapy for high-risk newly diagnosed transplant-ineligible multiple myeloma: Updated results from an open label, single-arm，phase 1 study（fumanba-2）

Abstract Equecabtagene Autoleucel (Eque-cel, IASO Bio), as a fully human BCMA chimeric antigen receptor (CAR) T-cell therapy, received approval in China for patients (pts) who had underwent at least three prior lines of therapy in June 2023. Since Mar 2022, researchers have been conducting the study to evaluate the efficacy and safety of Eque-cel in the treatment of transplant-ineligible pts with high-risk newly diagnosed MM (NDMM). Here we report the promising efficacy and safety profiles in FUMANBA-2 study (NCT05181501). FUMANBA-2, a phase 1, multi-center, single-arm clinical study, enrolled NDMM pts with high-risk features (defined as R-ISS stage III, double-hit, or triple-hit per mSMART 3.0 criteria). Pts would undergo 4 cycles of induction chemotherapy based on one of three regimens: Bortezomib-Lenalidomide-Dexamethasone, Bortezomib-Cyclophosphamide-Dexamethasone, or Bortezomib-Adriamycin-Dexamethasone. After the third cycle, the pts who were evaluated not eligible for Autologous Stem Cell Transplant (ASCT) underwent leukapheresis for Eque-cel manufacture. After lymphodepletion with Fludarabine-Cyclophosphamide, pts received a single infusion of Eque-cel at the dose of 1.0 x 106 CAR-T cells/Kg. Primary endpoint was the proportion of minimal residual disease (MRD)-negative (MRD−; sensitivity <10-5) and progression-free survival (PFS). Secondary endpoints included overall response rate, duration of response, safety, pharmacokinetics, and pharmacodynamics. As of May 13, 2025, a total of 16 pts (68.8% male; median aged 58.5 years [range, 51-69]) received Eque-cel infusion. Cytogenetics were detected in all pts with at least one high risk cytogenetic abnormalities (HRCA). 13 pts (81.3%) had double-hit, and 2 pts (12.5%) had triple-hit cytogenetics. 3 pts (18.8%) had R-ISS stage Ⅲ with a double-hit, and one patient (6.3%) had R-ISS stage Ⅲ with a triple-hit. 4 pts (25.0%) had extramedullary disease (EMD). With a median follow-up of 27.04 months (range: 10.8-36.1), all pts achieved at least VGPR with 93.8% (15/16) pts achieved sCR. All 16-pts achieved MRD-negativity within 1-month, and 80% (95% CI: 40.9%, 94.6%) pts achieved sustained MRD negativity over 24 months. The median PFS was not reached (NR). The PFS rates at 12-month, 18-month and 24-month were 87.5% (95%CI: 58.6%, 96.7%), 80.2% (95%CI: 50.1%, 93.2%) and 74.5% (95%CI: 45.4%, 89.6%), respectively. In pts with ≥ 2 HRCAs and EMD, 24-month PFS rates were 76.2% (95% CI:42.7%, 91.7%) and 75.0% (95% CI:12.8%, 96.1%), respectively. The median OS was NR, and OS rate at 24-month was 81.3% (95%CI: 52.5%, 93.5%). All 16-pts experienced treatment-related AEs, the most common of which were cytopenia, pyrexia, and infections. CRS occurred in 11 pts (68.8%), all of which were grade 1-2. The median time to CRS onset was 7 days (range: 2-9 days), with the median duration of 3 days (range: 1-8 days). No neurotoxic effects or ICANS was observed. Hypogammaglobulinemia occurred in 50% (8/16) of pts, and the median time to onset was 24 days (range: 8-79 days), with a median duration of 418 days (range: 22-797 days). The most common serious AEs were infections, which occurred in 7 pts (43.8%), with pneumonia being the most frequently reported (7 pts, 43.8%). Other infections included COVID-19, influenza, and meningitis. The expansion and persistence of Eque-cel in peripheral blood were evaluated in all 16 pts. The median peak vector copy number (VCN Cmax) of Eque-cel was 79681.30 copies/μg gDNA (range, 4519-130258 copies/μg gDNA). The median time to reach Cmax (Tmax) was 10 days (range: 7-21 days). The median area under the curve at day0-28 (AUC0-28d) was 691468.75 Day × Copies/μg DNA (range, 14552-1235359 Day × Copies/μg DNA). The median persistence of Eque-cel in peripheral blood was 75 days (range: 29-283 days) post-infusion. Soluble BCMA was cleared within 1 month post infusion in 81.25% (13/16) of pts. Secretion of inflammatory cytokines was also observed, with median peak levels of 58.59 pg/mL (range: 9.12-3017.83 pg/mL) for IL-6, 44.30 mg/L (range: 3.66-117.30 mg/L) for CRP, and 553.35 ng/mL (range: 68.10-2349.00 ng/mL) for ferritin. In conclusion, the current data suggest that Eque-cel could be a promising and effective treatment option for high-risk NDMM pts following induction therapy. However, longer follow-up and randomized controlled trials are necessary to further clarify the efficacy and safety of Eque-cel in this patient population.