Eque-cel Demonstrates High PFS in Newly Diagnosed, High-Risk Multiple Myeloma

Equecabtagene autoleucel (eque-cel; IASO Bio) has demonstrated efficacy and safety in treating patients with high-risk newly diagnosed multiple myeloma (NDMM), according to new data from the FUMANBA-2 study (NCT05181501).¹

Updated data from the study were presented at the European Hematology Association 2024 Hybrid Congress, held June 13-16 in Madrid, Spain, and virtually, by Professor Bing Chen, Nanjing Drum Tower Hospital.

“Eque-cel, as a novel fully human BCMA chimeric antigen receptor (CAR)-T therapy, has shown encouraging efficacy and safety in high-risk patients with NDMM who are ineligible for transplantation. This is the world’s first report on CAR-T therapy being used as a first-line treatment in this specific patient population. For NDMM patients who are not suitable for transplantation, the application of CAR-T therapy as a first-line treatment is expected to further improve the remission rate, extend survival, and improve patient prognosis compared to traditional chemotherapy and other targeted drug treatments. This allows us to see the application potential of eque-cel in the front-line treatment of MM. Advancing CAR-T therapy to the first line will provide patients with more diverse and promising treatment options. With further research and the continuous improvement of treatment strategies, we look forward to CAR-T therapy benefiting more patients in the future,” Professor Lijuan Chen, Jiangsu Province Hospital, said in a statement.¹

The multicenter, open-label, phase I, single-arm study FUMANBA-2 study was initiated by researchers, Professors Bing Chen and Lijuan Chen serving as primary investigators. Enrolled participants received4 cycles of induction treatment before receiving eque-cel. After the third induction treatment cycle, patients ineligible for autologous hematopoietic stem cell transplantation (ASCT) underwent peripheral blood mononuclear cell collection and subsequently received infusion of 1×10⁶ CAR-T/kg of eque-cel.

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As of January 25th, 2024, 16 participants with high risk cytogenic and NDMM received eque-cel therapy. Some participants also had double-hit (62.5%) or triple-hit (12.5%) disease, extramedullary disease (25%),and R-ISS stage III disease (37.5%).Median follow-up was 7.46 months (range, 2.8-18.1). Overall response rate (ORR) was 100% with a 93.8% stringent complete response rate (CR). Median progression-free survival (PFS) has not been reached and 12-month PFS was 84.4% (95% CI, 49.31-96.00). All participants achieved minimal residual disease (MRD) negativity, with 71.4% (95% CI, 25.8-92.0) maintaining MRD negativity for over 12 months.¹

Eque-cel had a favorable safety profile in the NDMM setting, with a 68.8% mild cytokine release syndrome (CRS) rate and no serious (above grade 3) CRS, immune effector cell-related neurotoxicity syndrome (ICANS), or other neurological toxicities. CRS occured at a median of 7 days after infusion (range, 2-9) and lasted for a median of 3 days (range, 1-8). Blood cell count reduction was the most common serious adverse event (AE). Serious infectious disease AEs had an incidence of 25%.¹

Looking at pharmacokinetics and pharmacodynamics, peak PAR copy time in peripheral blood was 10 days after infusion (range, 7-21) at a median peak of 79,681.299 copies/μg DNA. Most (81.25%) participants achieved clearance of free BCMA within 1 month after infusion and IL-6 and C-reactive protein peaked at the 7th and 10th days, respectively.Serum ferritin levels did not change significantly.¹

"High-risk NDMM patients have a poor prognosis in standard first-line treatment. For high-risk NDMM patients who do not meet the conditions for allogeneic stem cell transplant, eque-cel has shown superior efficacy and safety, achieving deep and sustained remission, with all patients achieving MRD negativity. This opens upa new approach to reverse the poor prognosis of high-risk myeloma patients. Moreover, compared with relapsed/refractory (rr) MM patients, the incidence and severity of CRS in high-risk NDMM patients treated with eque-cel are lower, showing a more favorable safety profile. We will further investigate the clinical benefits of eque-cel for high-risk newly diagnosed multiple myeloma patients with longer follow-up," Professor Bing Chen added.¹

Eque-cel is also being evaluated in patients with rrMM in the phase 1b/2 FUMANBA-1 study (NCT05066646). The trial previously showcased a 96% ORR, 74.3% CR, and a 91.1% very good partial response rate in 101 patients who were included in the efficacy analysis.²

REFERENCES
1. IASO Bio Presented New Data of FUCASO® (EquecabtageneAutoleucel) for the Treatment of High-risk Newly Diagnosed Multiple Myeloma in Oral Presentation at EHA 2024. News release. IASO Bio. June 16, 2024. https://www.iasobio.com/phone/info.php?id=241
2. Li C, Wang D, Song Y, et al. CT103A, a novel fully human BCMA-targeting CAR-T cells, in patients with relapsed/refractory multiple myeloma: Updated results of phase 1b/2 study (FUMANBA-1). Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #8025 Poster #17