Real-world outcomes with CAR-T therapy in relapsed/refractory multiple myeloma and severe renal failure: A propensity matched multi-center retrospective Study using trinetx database

Abstract

Abstract Introduction: Two BCMA CAR-T cell therapies ie Idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (cilta-cel) have been approved for use in relapsed/refractory multiple myeloma (RRMM). Safety and efficacy data with CAR-T cell use in RRMM in patients with severe renal failure is limited. Methods: A multicenter retrospective study was conducted using the TrinetX database network, a federated de-identified EMR network that included adult patients with a history of RRMM that received anti-BCMA CAR-T therapy between February 1st 2021 and July 1st 2025. Renal failure (RF) was defined as patients with an estimated glomerular filtration rate (eGFR) of less than 30ml/min or dialysis dependence. Statistical analysis is performed on the TrinetX research platform. Baseline patient demographics and clinical features were collected. The cohort was divided into two comparison groups, patients with and without severe renal impairment. Subsequently, propensity matching was done 1:1 (greedy) nearest neighbour without replacement with a caliper of 0.1, and outcomes were calculated with CAR-T cell therapy as the index event. Results: 998 patients were included in the analysis, the RF cohort had 66 patients and the non-RF cohort had 932 patients. The mean age at index of the RF group was 63.6 +/- 9.2, for the non-RF group was 65.0 +/- 9.3. 42.4% of the RF group were male, and 63.6% were white. 60.2% of the non-RF group were male and 73.6% were white. 450 received Ide-cel while 548 received Cilta-cel. The renal failure group had more extramedullary disease (7.6% vs 4.0%) at baseline. For lymphodepletion agents, cyclophosphamide was used in 83% of the renal impairment group vs 76% non-renal impairment group, Fludarabine was used in 78% vs 70%, bendamustine was used in 4% vs 5%. 1:1 propensity matching was done for age, sex, race, cardiovascular disease, stroke, chronic lung disease, obesity, ECOG yielding 128 patients in the final analysis (64 in each group). The mean follow up for the renal failure group was 445 days vs 524 days of the non-renal failure comparison group. The renal failure group had 15 deaths vs 11 in the comparison group [HR 1.468 (0.671-3.21), p=0.205], median overall survival (mOS) was 1,007 days in the RF group vs 1,013 days in the non-RF comparison group, p=0.396, any grade cytokine release syndrome (CRS) events were 33 in RF group vs 34 non-RF group [OR 0.939 (0.469-1.88) p=0.86, immune effector cell-associated neurotoxicity syndrome (ICANS) events were 16 vs 14 (OR 1.19 (0.525-2.701) p=0.676). Grade 3 or worse CRS and ICANS combined were fewer than 10 in each group. At baseline, 19 patients in the renal failure group were on dialysis while during the CAR-T therapy process, 20 were on dialysis. Within 30-days of treatment, neutropenia (ANC < 1000 cells/uL) was seen in 44 in the RF group vs 52 in non-RF group [OR 0.508 (0.223-1.153), p=0.103], thrombocytopenia (platelets < 50,000 cells/uL) was seen in 32 vs 31 [OR=1.065 (0.532-2.129), p=0.86] and anemia (Hb < 7.0 gm/dl) was seen in 11 vs 11 [OR=1.0 (0.399-2.505), p=1.0] Conclusion: Patients with renal failure have comparable outcomes and a comparable safety profile with CAR-T cell therapy in RRMM hence renal impairment should not exclude this cohort from CAR-T eligibility.