Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma.
Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma.
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DOI：
10.1182/blood.2020008865
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发表时间：
2021-06-10
期刊：
影响因子：
20.3
通讯作者：
Neelapu SS
中科院分区：
文献类型：
--
作者：
Strati P;Ahmed S;Furqan F;Fayad LE;Lee HJ;Iyer SP;Nair R;Nastoupil LJ;Parmar S;Rodriguez MA;Samaniego F;Steiner RE;Wang M;Pinnix CC;Horowitz SB;Feng L;Sun R;Claussen CM;Hawkins MC;Johnson NA;Singh P;Mistry H;Johncy S;Adkins S;Kebriaei P;Shpall EJ;Green MR;Flowers CR;Westin J;Neelapu SS
皮质类固醇用于治疗嵌合抗原受体（CAR）T细胞疗法的急性并发症。Strati等人研究了大B细胞淋巴瘤CAR T细胞治疗后皮质类固醇对患者结局的影响。使用更高剂量的类固醇与10个月无进展生存期缩短和总生存期降低相关。在大B细胞淋巴瘤中，较高的皮质类固醇累积剂量与CAR-T治疗后的早期进展相关。较高的累积剂量和长期早期皮质类固醇使用与CAR-T治疗后较短的总生存期相关。皮质类固醇通常用于管理与嵌合抗原受体（CAR）T细胞疗法相关的严重毒性。然而，目前尚不清楚它们的剂量、持续时间和时间是否会影响临床疗效。在这里，我们确定了皮质类固醇对接受标准治疗抗CD 19 CAR T细胞疗法治疗的复发性或难治性大B细胞淋巴瘤患者临床结局的影响。在评估的100例患者中，60例（60%）接受皮质类固醇治疗，以管理CAR T细胞治疗相关的毒性。中位累积地塞米松等效剂量为186 mg（范围，8-1803），皮质类固醇治疗的中位持续时间为9天（范围，1-30）。45例（75%）患者在第0 - 7天开始皮质类固醇治疗，15例（25%）患者在第7天后开始皮质类固醇治疗。中位随访10个月（95%置信区间，8-12个月）后，使用较高累积剂量的皮质类固醇与无进展生存期显著缩短相关。更重要的是，皮质类固醇累积剂量较高以及CAR T细胞输注后长期和早期使用与总生存期显着缩短相关。这些结果表明，皮质类固醇应以最低剂量和最短持续时间使用，并且在管理CAR T细胞治疗相关毒性的同时，应在临床可行时延迟开始使用。
Corticosteroids are used to treat the acute complications of chimeric antigen receptor (CAR) T-cell therapy. Strati et al examine the impact of corticosteroids on patient outcomes following CAR T-cell therapy for large B-cell lymphoma. Use of higher doses of steroids is associated with shorter progression-free survival at 10 months and decreased overall survival. Higher cumulative dose of corticosteroids is associated with early progression after CAR-T therapy in large B-cell lymphoma. Higher cumulative dose and prolonged, early corticosteroid use is associated with shorter overall survival after CAR-T therapy. Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy–associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy–associated toxicities.
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影响因子：
10.1
作者：
Liadi I;Singh H;Romain G;Rey-Villamizar N;Merouane A;Adolacion JR;Kebriaei P;Huls H;Qiu P;Roysam B;Cooper LJ;Varadarajan N
通讯作者：
Varadarajan N
DOI：
10.1056/nejmoa1707447
发表时间：
2017-12-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Neelapu SS;Locke FL;Bartlett NL;Lekakis LJ;Miklos DB;Jacobson CA;Braunschweig I;Oluwole OO;Siddiqi T;Lin Y;Timmerman JM;Stiff PJ;Friedberg JW;Flinn IW;Goy A;Hill BT;Smith MR;Deol A;Farooq U;McSweeney P;Munoz J;Avivi I;Castro JE;Westin JR;Chavez JC;Ghobadi A;Komanduri KV;Levy R;Jacobsen ED;Witzig TE;Reagan P;Bot A;Rossi J;Navale L;Jiang Y;Aycock J;Elias M;Chang D;Wiezorek J;Go WY
通讯作者：
Go WY
DOI：
10.1038/nrclinonc.2017.148
发表时间：
2018-01
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Neelapu SS;Tummala S;Kebriaei P;Wierda W;Gutierrez C;Locke FL;Komanduri KV;Lin Y;Jain N;Daver N;Westin J;Gulbis AM;Loghin ME;de Groot JF;Adkins S;Davis SE;Rezvani K;Hwu P;Shpall EJ
通讯作者：
Shpall EJ
影响因子：
82.9
作者：
Deng Q;Han G;Puebla-Osorio N;Ma MCJ;Strati P;Chasen B;Dai E;Dang M;Jain N;Yang H;Wang Y;Zhang S;Wang R;Chen R;Showell J;Ghosh S;Patchva S;Zhang Q;Sun R;Hagemeister F;Fayad L;Samaniego F;Lee HC;Nastoupil LJ;Fowler N;Eric Davis R;Westin J;Neelapu SS;Wang L;Green MR
通讯作者：
Green MR
影响因子：
45.3
作者：
Kochenderfer, James N.;Somerville, Robert P. T.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.