Itacitinib for the prevention of IEC therapy-associated CRS: results from the 2-part phase 2 INCB 39110-211 study.

This 2-part phase 2 study (INCB 39110-211) investigated the safety and efficacy of itacitinib, a potent, highly selective Janus kinase 1 inhibitor with broad anti-inflammatory activity, for the prevention of CRS and ICANS in patients who received commercial CD19-directed IEC therapy.

这项2部分的2期研究（INCB 39110-211）调查了伊塔西替尼的安全性和有效性，伊塔西替尼是一种强效、高度选择性的Janus激酶1抑制剂，具有广泛的抗炎活性，用于预防接受商业CD19导向的IEC治疗的患者的CRS和ICANS。

Patients in part 1 received 200 mg itacitinib once daily 3 days before IEC therapy (axicabtagene ciloleucel [axi-cel], brexucabtagene autoleucel, or tisagenlecleucel) through day 26 with guidelines for use of other CRS/ICANS interventions.

在第一部分中，患者在IEC治疗（axicabtagene ciloleucel [axi-cel]，brexucabtagene autoleucel或tisagenlecleucel）前3天开始每日一次口服200 mg itacitinib，持续至第26天，并有使用其他CRS/ICANS干预措施的指南。

In part 2 (double-blind), patients were randomized to receive 200 mg itacitinib twice daily or placebo 3 days before IEC therapy with axi-cel.

在第二部分（双盲）中，患者在IEC治疗前3天开始，被随机分配接受每日两次200 mg itacitinib或安慰剂，与axi-cel一起使用。

The primary end point was the proportion of patients with CRS grade ≥2 by day 14 using the American Society for Transplantation and Cellular Therapy consensus grading system.

主要终点是使用美国移植和细胞治疗学会共识分级系统，到第14天为止， CRS 等级≥2的患者比例。

Overall, 111 patients were enrolled (63 in part 1; 48 in part 2); 109 patients were analyzed for efficacy and 110 for safety.

总体而言，共有111名患者被纳入研究（第1部分63名；第2部分48名）；109名患者用于疗效分析，110名用于安全性分析。

By day 14, grade ≥2 CRS occurred in fewer patients on 200 mg twice daily itacitinib (17.4%) than on placebo (56.5%; P = .003).

在第14天时，接受200 mg每日两次伊他替尼治疗的患者中，2级或更高级别的细胞因子释放综合征（CRS）的发生率（17.4%）低于安慰剂组（56.5%；P = .003）。

The proportion of patients with grade ≥2 ICANS by day 28 was lower than with placebo (8.7% vs 21.7%).

在第28天时，2级或更高级别的免疫效应细胞相关神经综合征（ICANS）的患者比例低于安慰剂组（8.7%对比21.7%）。

Itacitinib was well tolerated, with pyrexia being the most common treatment-emergent adverse event(200 mg itacitinib twice daily, 43.5%; placebo, 50.0%), and itacitinib-related cytopenias were manageable.

伊他替尼耐受性良好，发热是最常见的治疗相关不良事件（每日两次200 mg伊他替尼，43.5%；安慰剂，50.0%），与伊他替尼相关的细胞减少症是可管理的。

Itacitinib did not affect IEC therapy efficacy (objective response rateat 6 months, 39.1% [200 mg itacitinib twice daily] vs 26.1% [placebo]).

伊他替尼并未影响IEC治疗的疗效（6个月时客观缓解率为39.1% [每日两次200 mg伊他替尼]对比26.1% [安慰剂]）。

This study was registered at www.clinicaltrials.gov as #NCT04071366.

本研究已在www.clinicaltrials.gov注册，注册号为#NCT04071366。