Abstract
Introduction:
Idecabtagene vicleucel (Ide-cel) is a BCMA-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory multiple myeloma (RRMM) and is approved by FDA after at least two lines of therapy (Otero et al. 2023). Early clinical trials, including the KarMMa study, had demonstrated promising efficacy with primarily inpatient use (Munshi et al. 2021). However, there has been an increasing interest in exploring its efficacy, safety, and feasibility with outpatient administration. We report real-world data on high incidence of early cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) after outpatient Ide-cel, highlighting the need for strict monitoring and new prophylactic strategies.
Methods:
IRB approval was obtained and EMR data of RRMM patients treated with outpatient Ide-cel was reviewed from 9/2019 to 7/2025. Baseline characteristics, toxicities, and treatment responses were collected and analyzed. Descriptive statistics summarized variables. Stratified analysis by hospitalization was done using independent t-tests for quantitative variables and chi-square tests for categorical variables. Unadjusted survival was analyzed with Cox regression. Statistical analyses were performed in SAS 9.4 with significance set at α = 0.05.
Results:
We identified 21 patients (median age 65 years- 38% male, 62% female) who underwent treatment with Ide-cel for RRMM at our institution. Baseline characteristics included median prior lines of therapy of 4, 42.9% with BMI ≥25, and 9.5% with ECOG ≥2, 76% with low hemoglobin, 9.5% with low albumin, and 33% with elevated ferritin.
CRS occurred in 76% (16/21) of patients. Grade 2 CRS was highest severity observed in 31% (5/16) of patients. 87.5% (14/16) of these patients received tocilizumab. Grade 1 ICANS was highest severity observed in 19% (4/21) of patients, requiring treatment with steroids with or without anakinra. All patients who experienced CRS and/or ICANS were hospitalized. Median time to admission following Ide-cel infusion was 1 day (range: 0-2). Median duration of hospitalization was 3 days (range: 1–90).
Hospitalized patients had lower mean albumin compared to those managed entirely outpatient (3.72 vs 4.18 g/dL, p=0.0127), suggesting a potential association between low nutritional status and risk of complications. Similarly, hospitalized patients had markedly low hemoglobin (9.64 vs 11.9 g/dL, p=0.0232), possibly reflecting higher baseline disease burden or impaired marrow reserve. Although not statistically significant (p=0.0954), ferritin was significantly higher in hospitalized patients (mean 723 ng/mL vs. 218 ng/mL), consistent with elevated inflammatory state or disease burden. The small sample size may have limited the power to detect statistical significance.
At a median follow up of 408 days (range: 35–953), the overall response rate was 86%, including 10 patients (48%) with a partial response and 8 (38%) with a complete response. Two patients (10%) had stable disease, and one (5%) had progressive disease as best response.
Overall mortality was 23.8% (5/21); all these patients required hospitalization. Causes of death included disease progression with concurrent infection in three patients (60%), disease progression alone in one patient (20%), and infection alone in one patient (20%). Out of these, one patient died within the first 30 days following Ide-cel infusion, due to complications from viral pneumonia.
No clinical or laboratory variable was significantly associated with overall survival or progression-free survival in unadjusted Cox proportional hazards models. While low albumin and hemoglobin, and elevated ferritin were associated with increased risk of hospitalization, none predicted survival, likely due to the limited sample size and event number.
Conclusion:
Outpatient administration of Ide-cel for RRMM is associated with a high incidence of early CRS and ICANS, often leading to unplanned hospitalizations. Lower baseline albumin and hemoglobin levels, along with elevated ferritin, may help identify patients at higher risk for complications. While these factors correlated with hospitalization risk, they did not predict survival in this small cohort. These findings highlight that early toxicities with Ide-cel are common in the outpatient setting and underscore the need for improved risk stratification and prophylactic strategies to enhance the safety of outpatient administration.
