IASO Biotherapeutics has presented compelling evidence that its fully human anti-BCMA CAR-T cell therapy, Equecabtagene Autoleucel (Eque-cel), maintains equivalent efficacy and safety in relapsed/refractory multiple myeloma (R/RMM) patients with renal impairment, addressing a critical treatment gap for this vulnerable patient population.
Breakthrough Results in Renal Impairment Patients
The pivotal phase 2 FUMANBA-1 study enrolled 91 subjects without prior CAR-T treatment, with a median follow-up of 18.07 months. Among these patients, 28 had renal impairment with creatinine clearance (CrCl) between 40 and 70 ml/min, while 63 patients had normal kidney function with CrCl >70 ml/min.
The results demonstrated that patients with renal impairment achieved responses as rapid and deep as those without kidney dysfunction. Long-term efficacy in the renal impairment group was not inferior to the non-renal impairment group, with both groups developing cytokine release syndrome (CRS) at similar rates. Notably, no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in the renal impairment group, compared to one grade 2 case in the non-renal impairment group.
"In the past, we were concerned about the potential intolerance of R/R MM patients with impaired renal function to CAR-T treatment," stated Professor Lugui Qiu from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. "The current study confirmed that even in patients with renal impairment, Eque-cel can induce rapid, deep, and durable remission, with efficacy comparable to that of patients without renal impairment."
CAR-T Cell Persistence Drives Clinical Outcomes
A separate post-hoc analysis of 107 patients from the FUMANBA-1 study, presented at the 66th American Society of Hematology Annual Meeting, revealed the critical importance of CAR-T cell persistence for optimal disease control. With a median follow-up of 24.67 months, the study examined the relationship between CAR-T cell persistence and clinical outcomes.
The analysis introduced the concept of an "efficacy-to-target ratio," measured by the ratio of vector copy number (VCN) duration to baseline soluble B-cell maturation antigen (sBCMA) levels. The median efficacy-to-target ratio for the 107 subjects was 1.05 (days*mL/ng). Patients with lower ratios had significantly higher risks of disease progression, with a hazard ratio for time to progression of 3.07 (95% CI: 1.51–6.24, p=0.0011) and for progression-free survival of 2.3 (95% CI: 1.27–4.14, p=0.0045).
The ongoing remission group showed a longer median VCN duration compared to those with progression or relapse (12.52 months vs 9.03 months). Among baseline characteristics, only previous autologous stem cell transplantation and anti-drug antibodies as post-infusion factors were significantly associated with Eque-cel persistence.
Exceptional Efficacy and Safety Profile
The therapy achieved remarkable clinical outcomes, with a 97.8% MRD negativity rate and a sustained MRD negativity rate of 81.7% at 12 months post-infusion. The median duration of CAR-T cells for Eque-cel was 419 days, which researchers identified as a key factor in achieving these high response rates.
Safety data showed that only 14 of 107 subjects exhibited an aplastic neutrophil recovery phenotype, characterized by persistent neutrophil counts below 500/μl for 14 days or more. This phenotype did not significantly affect VCN duration compared to patients without the condition, indicating that long-term persistence of Eque-cel does not increase hematological toxicity.
"The data demonstrated that subjects with an efficacy-to-target ratio above the median value had a better prognosis in terms of PFS and TTP," explained Dr. Jie Chen, Chief Medical Officer of IASO Bio. "These findings further confirmed the positive effect of long-term CAR-T cells persistence in achieving sustained remission."
Advancing Treatment Options
The FUMANBA-1 study is a single-arm, open-label phase 1b/2 registrational clinical study conducted across 14 Chinese centers. The trial enrolled patients with R/RMM who had received at least three lines of prior therapy, including proteasome inhibitors and immunomodulatory agents-based chemotherapy regimens.
Equecabtagene Autoleucel received Biologics License Application approval from China's National Medical Products Administration in June 2023 and U.S. FDA IND approval for R/RMM treatment in December 2022. IASO Bio has initiated a randomized controlled Phase 3 clinical study of this therapy for second- and third-line multiple myeloma treatment.
The findings suggest that baseline sBCMA levels do not negatively affect the persistence and efficacy of Eque-cel, and the efficacy-to-target ratio may serve as a biomarker for future treatment planning. This research provides valuable insights for expanding CAR-T therapy access to multiple myeloma patients with complex clinical presentations, including those with renal impairment who were previously considered challenging to treat.
