Objectives

CAR T cell therapy has generally been limited to inpatient treatment. Infusion and management of CAR T cell therapy in the outpatient setting may lead to wider use in nonuniversity centers and improved access. We report on patients (pts) with R/R large B cell NHL treated with liso-cel in the outpatient setting in TRANSCEND NHL 001 (NCT02631044) and two phase 2 studies (≥3rd-line therapy: OUTREACH, NCT03744676; 2nd-line TNE: PILOT, NCT03483103).

Methods

Eligible pts had R/R large B cell NHL (TRANSCEND/OUTREACH: ≥2 lines of prior therapy and ECOG PS ≤1; PILOT: 1 line of prior therapy and deemed TNE for autologous hematopoietic stem cell transplant based on ECOG PS, organ function, or age). After lymphodepletion with fludarabine/cyclophosphamide, liso-cel was administered. All studies allowed outpatient treatment at nonuniversity (OUTREACH) or university and nonuniversity medical centers (TRANSCEND/PILOT), with hospitalization at the first sign of fever or neurological events (NEs) per management guidelines.

Results

At data cutoff, 37 pts across studies received liso-cel on study Day 1 and were monitored as outpatients, including pts aged ≥65 years (n = 15) and those with SPD ≥50 cm² (n = 10) or LDH ≥500 UL (n = 2). Results are shown in the Table. Sixteen pts had any grade cytokine release syndrome (CRS) and 12 had any grade NEs (19 pts had CRS and/or NEs). Only 2 pts had had grade 3 or 4 CRS or NEs, which were reversible. Three pts received tocilizumab and corticosteroids for CRS and/or NEs; none received tocilizumab alone. Overall, 59% of pts (n = 22/37) required hospitalization at any time; all were from TRANSCEND or OUTREACH. Of 37 pts, 3 (8%) were admitted on study Day 3 or earlier (all for CRS) and 1 (3%) required ICU-level care (length of stay, 3 days). Median time to hospitalization post treatment was 5 (range, 2‒22) days; median length of stay was 6 (range, 2‒23) days. Overall, 41% of pts (15/37), including all 5 pts from PILOT, did not require hospitalization in the first 29 days post liso-cel infusion. Across all studies, most pts achieved an objective response (76%), including complete responses.

Conclusions

A subset of pts with R/R large B cell NHL were successfully treated with liso-cel and monitored for CAR T cell–related toxicity in the outpatient setting, including elderly pts and pts with high tumor burden. Incidences of severe CRS, NEs, and early hospitalization were low; 41% of pts did not require hospitalization in the first month post treatment. Most pts achieved an objective response.

中文翻译：

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Lisocabtagene Maraleucel（liso-cel）的门诊治疗在3项正在进行的复发/难治性（R / R）大B细胞非霍奇金淋巴瘤（NHL）临床研究中，包括二线移植不合格（TNE）患者：Transcend NHL 001，外展和飞行员

目标

CAR T细胞疗法通常仅限于住院治疗。门诊环境中CAR T细胞疗法的输注和管理可能会导致在非大学中心的更广泛使用和更好的获取机会。我们在门诊中通过TRANSCEND NHL 001（NCT02631044）和两项2期研究（≥3线治疗：OUTREACH，NCT03744676； 2线）报道了用liso-cel治疗的R / R大B细胞NHL患者（点） TNE：飞行员，NCT03483103）。

方法

符合条件的患者具有R / R大B细胞NHL（TRANSCEND / OUTREACH：≥2系既往治疗且ECOG PS≤1; PILOT：1系既往治疗且被视为TNE用于基于ECOG PS，器官功能的自体造血干细胞移植或年龄）。用氟达拉滨/环磷酰胺进行淋巴清除后，给予liso-cel。所有研究均允许在非大学（OUTREACH）或大学和非大学医疗中心（TRANSCEND / PILOT）进行门诊治疗，并根据管理指南在出现发烧或神经系统事件（NEs）的第一个迹象时住院。

结果

在数据截止时，在研究的第1天，接受研究的37位患者接受了liso-cel并作为门诊患者进行监测，包括年龄≥65岁（n = 15）和SPD≥50cm ^2的患者。（n = 10）或LDH≥500 UL（n = 2）。结果示于表中。有16位患者有任何级别的细胞因子释放综合征（CRS），有12位患者具有任何等级的NEs（19位患者具有CRS和/或NEs）。只有2位患者具有3级或4级CRS或NE，这是可逆的。3名患者接受了托珠单抗和糖皮质激素治疗CRS和/或NEs；没有人单独接受托珠单抗治疗。总体而言，有59％的患者（n = 22/37）随时需要住院；全部来自TRANSCEND或OUTREACH。在37名患者中，有3名（8％）在研究的第3天或更早时入院（均为CRS），其中1名（3％）需要ICU级护理（住院时间为3天）。治疗后住院的中位时间为5天（2-22天）。中位住院时间为6天（2-23天）。总体而言，在lisocel输注后的前29天内，有41％的患者（15/37），包括来自PILOT的所有5分，都不需要住院。

结论

带有R / R大B细胞NHL的部分患者已成功通过liso-cel治疗，并在门诊环境中监测了CAR T细胞相关毒性，包括老年患者和高肿瘤负荷患者。严重的CRS，NE和早期住院的发生率很低。在治疗后的第一个月，有41％的患者不需要住院。大多数患者取得了客观的回应。