Hoogland Aasha I, Barata Anna, Li Xiaoyin, Irizarry-Arroyo Nathaly, Jain Michael D, Welniak Taylor, Rodriguez Yvelise, Oswald Laura B, Gudenkauf Lisa M, Chavez Julio C, Khimani Farhad, Lazaryan Aleksandr, Liu Hien D, Nishihori Taiga, Pinilla-Ibarz Javier, Shah Bijal D, Crowder Sylvia L, Parker Nathan H, Carson Tiffany L, Vinci Christine E, Pidala Joseph A, Logue Jennifer, Locke Frederick L, Jim Heather S L
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida.
Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
Transplant Cell Ther. 2024 Dec;30(12):1219.e1-1219.e11. doi: 10.1016/j.jtct.2024.09.013. Epub 2024 Sep 19.
Chimeric antigen receptor (CAR) T-cell therapy has transformed survival outcomes in patients with relapsed and refractory large B-cell lymphoma (LBCL), but it is associated with a variety of side effects. This study examined changes in patient-reported quality of life (QoL) and toxicities, as well as risk factors for worse QoL and toxicities, in the first year after treatment. Patients with LBCL completed questionnaires assessing QoL and toxicity severity before infusion, and 90, 180, and 360 days after infusion. Mixed models were used to examine changes in QoL and toxicities over time, and clinical moderators of change in QoL and toxicities. Patients reported improvements in physical functioning and fatigue in the year after treatment (P values <.01), but there were no changes in pain, anxiety, or depression over time. Patients with active disease at day 90 reported more physical dysfunction at all postinfusion timepoints (Ps ≤ .01) compared to patients who responded to treatment. Similarly, patients with active disease at day 90 reported worsening depression over time, such that at day 360, depressive symptoms were worse for patients with active disease than patients without active disease (P = .02). Patients treated with 4+ lines of prior therapy reported worsening pain and anxiety over time, such that at day 360, both pain and anxiety were significantly worse for patients previously treated with 4 of more lines of therapy than patients treated with fewer lines of therapy (Ps ≤ .01). Regarding toxicities, patients reported decreasing overall toxicity burden up to day 180, with subsequent worsening at day 360 (P = .02). Most patients reported at least one or two grade 2 toxicities at each timepoint. Patients demonstrated unchanging or improved QoL after treatment with CAR T-cell therapy, but active disease and greater prior lines of therapy were associated with worse QoL outcomes over time. Toxicity severity also improved during the first 6 months post-treatment, but worsened thereafter, particularly among patients with active disease after treatment.
嵌合抗原受体（CAR）T细胞疗法改变了复发难治性大B细胞淋巴瘤（LBCL）患者的生存结局，但它也伴随着多种副作用。本研究调查了治疗后第一年患者报告的生活质量（QoL）变化、毒性反应，以及生活质量和毒性反应变差的风险因素。LBCL患者在输注前、输注后90天、180天和360天完成了评估生活质量和毒性严重程度的问卷调查。使用混合模型来研究生活质量和毒性反应随时间的变化，以及生活质量和毒性反应变化的临床调节因素。患者报告治疗后一年内身体功能和疲劳状况有所改善（P值<.01），但疼痛、焦虑或抑郁症状随时间没有变化。与治疗有反应的患者相比，在第90天仍有活动性疾病的患者在所有输注后时间点的身体功能障碍更多（P值≤.01）。同样，在第90天仍有活动性疾病的患者抑郁症状随时间加重，以至于在第360天，有活动性疾病的患者的抑郁症状比无活动性疾病的患者更严重（P =.02）。接受过4线及以上既往治疗的患者疼痛和焦虑症状随时间加重，以至于在第360天，接受过4线及以上治疗的患者的疼痛和焦虑症状比接受治疗线数较少的患者明显更严重（P值≤.01）。关于毒性反应，患者报告在第180天之前总体毒性负担逐渐减轻，随后在第360天加重（P =.02）。大多数患者在每个时间点报告至少有一到二级毒性反应。接受CAR T细胞治疗后患者的生活质量保持不变或有所改善，但活动性疾病和更多的既往治疗线数与随时间更差的生活质量结局相关。毒性严重程度在治疗后的前6个月也有所改善，但此后恶化，特别是在治疗后有活动性疾病的患者中。
