Introduction

Use of Axi-cel in patients with refractory and relapsed (R/R) large B-cell lymphoma (BCL) is associated with significant inpatient and outpatient resource utilization, which has not been systematically evaluated. We characterized resources used around Axi-cel infusion and identified factors that lead to longer hospitalization during the first 100 days of therapy.

Methods

We reviewed medical records of consecutive adult patients with R/R large BCL treated with Axi-cel at our center from May 2018 to June 2019. Resource utilization data were collected across 3 time points and sorted into categories that reflect inpatient and outpatient resources (Table 1). We evaluated the number of “days alive and out-of-hospital through Day 100 from cell infusion” (DAOH₁₀₀), as a surrogate for institutional resource utilization and to identify factors leading to prolonged hospitalization.

Results

Axi-cel was used in 27 patients with R/R BCL; 18 were male (67%) with median age 63 years (IQR 48-68), median IPI 2 (IQR 2-3), 20 (74%) had ECOG PS < 2 and 24 (89%) had stage ≥ 3 disease. Median number of prior therapies was 3 (IQR 3-5) and HCT-CI score was 2 (IQR 0-3).

The median length of stay for the initial hospitalization was 13 days (IQR 9-16) and through Day 100 was 16 days (IQR 12-30). Eight (30%) patients required ICU admission for a median of 2.5 days (IQR 1-9.8), while vasopressors, mechanical ventilation and dialysis were used in 6 (22%), 3 (11%) and 2 (7%) patients respectively. Patients had a median of 5 (IQR 3-7) outpatient clinic visits through Day 100. The median number of radiological studies and cardiac/neurological evaluation through Day 100 were 6 (IQR 4-11) and 1 (IQR 0-6) respectively. Pharmaceutical resources are summarized in Table 1.

Cytokine release syndrome (CRS) and CAR-related encephalopathy syndrome (CRES) were seen in 22 (82%) and 20 (74%) patients, with ≥ Grade 2 CRS (Lee, et al) and CRES (CARTOX-10) in 16 (59%) and 13 (48%) patients respectively. By Day 100, 24 (89%) patients were alive and 4 (15%) had disease progression. The median DAOH₁₀₀ were 84 days (IQR 69-88). DAOH₁₀₀ were higher in patients with favorable ECOG PS (< 2) compared to unfavorable (≥ 2) (median DAOH₁₀₀ 86 vs 70 days, P=0.04). Patients with no or mild CRES (< grade 2) had higher DAOH₁₀₀ compared to those with moderate to severe CRES (≥ grade 2) (median DAOH₁₀₀ 86 vs 70 days, P=0.01). DAOH₁₀₀ did not differ with respect to age, HCT-CI score, IPI, number of prior therapies or CRS grade (Table 2).

Conclusion

In this single institutional experience of using Axi-cel therapy for R/R BCL, we demonstrated utilization of substantial resources in terms of hospitalization, ICU stay, diagnostic studies and pharmaceutical products. Patients with favorable PS and no or minimal CRES spend a higher number of days at home (alive and out-of-hospital), in first 100 days of Axi-cel therapy.

中文翻译：

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Axicabtagene Ciloleucel（Axi-cel）顽固性和复发性B细胞淋巴瘤患者的资源利用和延长住院治疗的因素

介绍

在顽固性和复发性（R / R）大B细胞淋巴瘤（BCL）患者中使用Axi-cel与大量的住院和门诊资源利用有关，尚未进行系统评估。我们对围绕Axi-cel输注使用的资源进行了分类，并确定了在治疗的前100天内导致较长住院时间的因素。

方法

我们于2018年5月至2019年6月在我们中心回顾了接受Axi-cel治疗的连续成年R / R大型BCL成人患者的病历。资源利用率数据收集了3个时间点，并按反映住院和门诊资源的类别进行分类（表1）。我们评估了“从细胞注入到第100天的存活天数和住院日数”（DAOH ₁₀₀）的数目，作为机构资源利用的替代指标，并确定了导致住院时间延长的因素。

结果

Axi-cel用于27例R / R BCL患者；男性18位（67％），中位年龄63岁（IQR 48-68），中位IPI 2（IQR 2-3），20位（74％）ECOG PS <2、24位（89％）≥3期。先前治疗的中位数为3（IQR 3-5），HCT-CI评分为2（IQR 0-3）。

最初住院的中位住院时间为13天（IQR 9-16），到第100天的住院时间为16天（IQR 12-30）。八名（30％）患者需要接受ICU入院，中位数为2.5天（IQR 1-9.8），而6例（22％），3例（11％）和2例（7％）患者使用了血管加压药，机械通气和透析分别。到第100天，患者的中位门诊次数为5（IQR 3-7）。到第100天，放射学和心脏/神经系统评估的中位数分别为6（IQR 4-11）和1（IQR 0-6）。 。药物资源汇总于表1。

在22例（82％）和20例（74％）的患者中发现了细胞因子释放综合征（CRS）和CAR相关性脑病综合征（CRES），其中CRS≥2级（Lee等）和CRES（CARTOX-10）。分别有16位（59％）和13位（48％）患者。到第100天，有24名（89％）患者还活着，有4名（15％）患者病情恶化。DAOH ₁₀₀的中位数为84天（IQR 69-88）。ECOG PS良好（<2）的患者的DAOH ₁₀₀高于不良（≥2）的患者（DAOH ₁₀₀ 86 vs 70天，中位数P = 0.04）。没有中度CRES（<2级）的患者的DAOH ₁₀₀高于中度至重度CRES（≥2级）的患者（DAOH中位数₁₀₀ 86 vs 70天，P ＝ 0.01）。DAOH ₁₀₀在年龄，HCT-CI评分，IPI，既往治疗次数或CRS等级方面无差异（表2）。

结论

在使用Axi-cel疗法治疗R / R BCL的单一机构经验中，我们证明了在住院，ICU住院，诊断研究和药品方面的大量资源利用。在Axi-cel治疗的前100天内，PS良好且CRES没有或仅有最小CRES的患者在家里的时间（存活时间和院外时间）更长。