Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed B-cell lymphomas treatment. Its use is complicated by cytokine release syndrome (CRS) and immune effector-cell associated neurotoxicity syndrome (ICANS) resulting in heightened healthcare resource utilization through increased patient morbidity, hospitalization, and intensive care unit (ICU) transfers. The prevention of CRS and ICANS is the goal to facilitate improved patient safety and efficient resource allocation following CAR-T. In April 2024, our institution adopted a quality improvement (QI) initiative utilizing primary prophylactic anakinra 100 mg administered intravenously (IV) daily for 7 days starting on the day of infusion to mitigate CRS and ICANS. Through emerging evidence, we hypothesized prophylactic anakinra may reduce CRS and ICANS without compromising CAR-T efficacy. However, this practice of prophylactic anakinra remains off-label and its impact on our patient population remains unknown.

Methods: This observational, single-center retrospective cohort QI analysis evaluated consecutive B-cell lymphoma patients treated with axicabtagene ciloleucel (axi-cel) or brexucabtagene autoleucel (brexu-cel) anti-CD19 CAR-T therapy the year before (March 1, 2023 to March 31, 2024) and the year after (April 1, 2024 to April 30, 2025) the implementation of anakinra prophylaxis. Outcome measures included incidence and severity of CRS and ICANS, ICU admissions, medications for CRS and ICANS, infection rates, hematologic toxicities, and supportive care resource utilization. The objective is to evaluate the clinical and resource impact of our prophylactic anakinra QI strategy.

Results: A total of 20 patients without anakinra prophylaxis (median age 62 years; axi-cel, n=16; brexu-cel, n=4; large B-cell lymphoma (LBCL), 80%) and 25 patients with anakinra prophylaxis (median age 62 years; axi-cel, n=23; brexu-cel, n=2; LBCL, 72%) were analyzed. Severe (grade ≥3) CRS was absent in both groups; severe (grade ≥3) ICANS occurred in 20% without prophylaxis and 0% with prophylaxis. All-grade ICANS was reduced from 65% to 40% with prophylaxis. ICU admission occurred in 15% (n=3), exclusively in the non-prophylaxis group for severe ICANS. Treatment anakinra (i.e., 100 mg IV every 6 hours) was required in 60% patients without prophylaxis (median 31 [interquartile range (IQR) 20-39] doses) and 88% patients with prophylaxis (median 25 [IQR 20-36] doses). Tocilizumab use was decreased from 65% to 32% with anakinra prophylaxis, both groups requiring a median of 1 dose. Dexamethasone use was decreased from 100% in non-prophylaxis to 88% in prophylaxis group, with a median total cumulative dose of 115 (IQR 68-265) and 95 (IQR 45-173) mg, respectively. Infection rates were lower with prophylaxis from 70% to 40%. Day 30 incidences of anemia (grade ≥2) were 50% and 25%; neutropenia (grade ≥3) were 25% and 8%; and thrombocytopenia (grade ≥2) were 65% and 40% in non-prophylaxis and prophylaxis groups, respectively. At day 30, ongoing blood transfusions were required in 20% (n=4) and 8% (n=2); and ongoing granulocyte-colony stimulating factor use were required in 65% (n=13) and 36% (n=8) in non-prophylaxis and prophylaxis groups, respectively. Day 90 overall disease response rates were comparable between groups. Accounting for all CRS and ICANS medication expenses, the addition of prophylactic anakinra was estimated to increase drug costs by $171 (Canadian dollars) per patient.

Conclusions: This QI initiative suggests prophylactic anakinra enhances patient safety by reducing severe ICANS and treatment-related toxicities, while improving healthcare efficiency through fewer ICU admissions and decreased reliance on high-cost therapies such as tocilizumab. Although introducing prophylactic anakinra adds a modest upfront medication cost, these expenses may be offset by downstream savings from decreased healthcare resource utilization. By mitigating severe toxicities and lowering the need for emergent interventions, anakinra prophylaxis may facilitate safer transitions to outpatient CAR-T therapy delivery. Given its favorable safety profile and minimal cost impact, prophylactic anakinra represents a scalable, cost-effective approach that could support the broader implementation of outpatient CAR-T therapy delivery models. Prospective validation is warranted to confirm these findings, to identify ideal dosing and evaluate their applicability across health systems.

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2025
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