Piatek Caroline, Murakhovskaya Irina, Karaouni Alia, Miles Gandarvaka, Bozzi Sylvie, Heller Carrie, Lucia Jacqueline, Patel Reena, Ward Brad, Yoo Ronnie, Gertz Morie
Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases USC Norris Comprehensive Cancer Center Los Angeles California USA.
Department of Hematology and Oncology Division of Hematology Montefiore Medical Center/Albert Einstein College of Medicine Bronx New York USA.
EJHaem. 2025 Jul 12;6(4):e70082. doi: 10.1002/jha2.70082. eCollection 2025 Aug.
Rituximab is used off-label for treating cold agglutinin disease (CAD) in the United States; however, real-world data on its use are limited.
This study examined (1) treatment patterns, (2) prespecified safety outcomes, and (3) changes in hemolytic markers post rituximab infusion (threshold change from baseline: hemoglobin [Hb]: ≥2 g/dL increase; bilirubin or lactate dehydrogenase [LDH]: ≥50% decrease). Of 611 patients with CAD (Cohort 1) identified using Optum's de-identified Market Clarity database (2007-2021), 94 who received rituximab (Cohort 2) were included.
Rituximab was predominantly used as monotherapy; the median (interquartile range; IQR) number of rituximab courses per patient was 1.0 (1.0-2.0); 24 (25.5%) patients had ≥1 incomplete course and 37 (39.4%) required blood transfusion. The incidence rate (IR) of serious infections per 1000 patient-years (95% CI) post rituximab initiation was three times higher than before rituximab initiation (637.1 [242.2-1032.0] vs. 245.4 [125.1-365.6]). Cohort 2 had a similar IR of thromboembolic events and slightly higher hospitalization rates and deaths than Cohort 1. After the first course of rituximab, 69.5% (41/59), 59.6% (28/47), and 31.3% (10/32) of patients reached thresholds for Hb, bilirubin, and LDH, respectively. The median (IQR) duration of improvement was 44 (13.3-90.8), 98 (29.0-257.0), and 93 (21.3-161.8) days for Hb, bilirubin, and LDH, respectively. Reversal from threshold occurred in 68.3% (28/41), 53.6% (15/28), and 80.0% (8/10) of patients for Hb, bilirubin, and LDH, respectively.
Rituximab showed a limited durability of response and an increased risk of infection, suggesting the need for more effective and safer treatment options.
: The authors have confirmed clinical trial registration is not needed for this submission.
在美国，利妥昔单抗被用于治疗冷凝集素病（CAD），但属于超说明书用药；然而，关于其使用的真实世界数据有限。
本研究调查了（1）治疗模式，（2）预先设定的安全结局，以及（3）利妥昔单抗输注后溶血标志物的变化（与基线相比的阈值变化：血红蛋白[Hb]：增加≥2g/dL；胆红素或乳酸脱氢酶[LDH]：降低≥50%）。利用Optum的去识别化市场清晰度数据库（2007 - 2021年）识别出611例CAD患者（队列1），其中94例接受了利妥昔单抗治疗的患者被纳入（队列2）。
利妥昔单抗主要作为单一疗法使用；每位患者利妥昔单抗疗程的中位数（四分位间距；IQR）为1.0（1.0 - 2.0）；24例（25.5%）患者有≥1个不完整疗程，37例（39.4%）患者需要输血。利妥昔单抗开始使用后每1000患者年（95%CI）严重感染的发生率比开始使用利妥昔单抗前高出三倍（637.1[242.2 - 1032.0]对245.4[125.1 - 365.6]）。队列2的血栓栓塞事件发生率与队列1相似，住院率和死亡率略高于队列1。在第一个利妥昔单抗疗程后，分别有69.5%（41/59）、59.6%（28/47）和31.3%（10/32）的患者达到了Hb、胆红素和LDH的阈值。Hb、胆红素和LDH改善的中位（IQR）持续时间分别为44（13.3 - 90.8）天、98（29.0 - 257.0）天和93（21.3 - 161.8）天。分别有68.3%（28/41）、53.6%（15/28）和80.0%（8/10）的患者Hb、胆红素和LDH从阈值水平逆转。
利妥昔单抗显示出反应的持久性有限且感染风险增加，这表明需要更有效和更安全的治疗选择。
作者已确认本投稿无需进行临床试验注册。
