P-100: Outcomes of R/R MM Patients with Renal Function Impairment Treated with Eque-cel in the Pivotal Phase 2 FUMANBA-1 Study

Introduction: R/R MM and renal impairment(RI) tend to be more challenging to manage. Administration of anti-myeloma treatment is important to reduce the production of monoclonal FLC. Equecabtagene Autoleucel (Eque-cel ) has demonstrated a favorable safety and efficacy profile in heavily pretreated RRMM patients. However, the impact of RI on the outcome of Eque-cel remains unknown. Especially when lymphodepletion (LD) is often adjusted in RI, and LD is also associated with the outcome. We evaluated outcomes of RRMM patients with RI treated with Eque-cel in FUMANBA-1 study (NCT05066646), including pharmacokinetics, efficacy, safety, and renal function changes.

Methods: A retrospective analysis was conducted. Patients were divided into RI group and non-RI group, based on whether the creatinine clearance (CrCl) was≤70 ml/min at the time of CAR-T therapy. Baseline characteristics were compared between the two groups. Pharmacokinetics, and efficacy endpoints, including ORR, CR, PFS, OS, MRD negativity and duration of MRD negativity, were evaluated. As for safety data, we mainly analyzed CRS and ICANS, cytopenia. And changes of renal function were analyzed.

Results: With a median follow up of 18.07months, 91 patients without prior CAR-T received eque-cel, of which 28 had RI with CrCl between 40 and 70ml/min and 63 belonged to non-RI group with CrCl >70ml/min. Most baseline characteristics in RI group were comparable to non-RI group.12 patients underwent LD adjustment in the RI group. The pharmacokinetics in the LD adjustment group was comparable to the standard LD group. RI group could also achieve response as rapid and deep as the non-RI group. The long-term efficacies for RI group were also not inferior. The specific data is shown in the table below.

Baseline Characteristics & Efficacy	RI(N=28)	non-RI(N=63)
High-risk genetic factors	71%	70%
ISS stage III	18%	11%
EMD	18%	8%
ECOG 1	89%	68%
ORR	100%	98%
CR/sCR	79%	84%
D14 ORR	79%	64%
D14 MRD negativity	62%	57%
12-month MRD negativity maintaining	78%	83%
12-month PFS	77%	89%
12-month OS	86%	96%
PK	RI with LD adjustment（N=12)	RI without LD adjustment（N=16）
Tmax (days）	12	11
median Cmax(copies/μ g DNA)	120636	99603
median AUC0-28(day*copies/μ g DNA)	1076206	986429
median AUC0-last(day*copies/μ g DNA)	1902160	1775274

No significant CRS incidence difference was observed between the two groups. Only 1 grade 2 ICANS in the non-RI group, no ICANS occurred in RI group. A little higher prevalence of short-term severe cytopenia occurred in the RI group but recovered equally by day 60. 73.2% and 58.8% of all patients treated with eque-cel experienced improvement in CrCl compared to baseline at 14 days and 3 months post infusion.

Conclusions: In the FUMANBA-1 study,RRMM patients with RI could also achieve similarly rapid, deep, and durable response with eque-cel treatment without compromising safety status. Renal function could also be improved due to the clearance of myeloma cells by eque-cel.
Thanks to professor Lugui Qiu,the corresponding author of this paper.