Vitamin D Insufficiency and Clinical Outcomes with Chimeric Antigen Receptor T-Cell Therapy in Large B-cell Lymphoma.
Vitamin D Insufficiency and Clinical Outcomes with Chimeric Antigen Receptor T-Cell Therapy in Large B-cell Lymphoma.
复制标题
DOI：
10.1016/j.jtct.2022.08.001
复制
发表时间：
2022-11
影响因子：
3.2
通讯作者：
Shouval R
中科院分区：
文献类型：
--
作者：
Nath K;Tomas AA;Flynn J;Fein JA;Alperovich A;Anagnostou T;Batlevi CL;Dahi PB;Fingrut WB;Giralt SA;Lin RJ;Palomba ML;Peled JU;Salles G;Sauter CS;Scordo M;Fraint E;Feuer E;Shah N;Slingerland JB;Devlin S;Shah GL;Gupta G;Perales MA;Shouval R
维生素D不足是新诊断的大B细胞淋巴瘤（LBCL）预后不良的潜在可改变风险因素。然而，目前尚不清楚循环维生素D浓度在用CD 19定向嵌合抗原受体T细胞疗法（CAR-T）治疗的复发性/难治性LBCL中的作用。这是一项单中心、观察性研究，在111例成人复发性/难治性LBCL患者中评估了CAR-T前25-羟基维生素D（25-OHD）状态与100天完全缓解、无进展生存期、总生存期和CAR-T相关毒性的相关性。根据内分泌学会指南，维生素D不足定义为≤30 ng/ml。CAR-T前25-羟基维生素D浓度中位数为24 ng/ml（IQR 18-34）。维生素D不足的患者（≤30 ng/ml; n=73 [66%]）明显比维生素D充足的患者（>30 ng/ml; n=38 [34%]）年轻（p=0.039）。维生素D不足队列富含新发LBCL作为组织学亚型（p=0.026），并且具有较高比例的tisagenlecleucel作为CAR-T产品（p=0.049）。两组之间的基线特征没有其他显著差异。与维生素D充足患者相比，维生素D不足患者的100天完全缓解率分别为55%和76%（p=0.029），2年总生存率分别为41%和71%（p=0.061）。在多变量分析中，维生素D不足与100天完全缓解（OR 2.58 [1.05-6.83]; p=0.045）和总生存率（HR 2.24 [1.08-4.66]，p=0.030）显著相关。在tisagenlecleucel的接受者中，维生素D不足与输注CAR-T产品的细胞活力显著降低相关（p=0.015）。最后，治疗前维生素D不足不能预测随后的CAR-T相关毒性。这是第一份证明维生素D不足与CAR-T接受者的不良临床结局相关的报告。进一步研究这一发现的机制见解，以及维生素D补充剂在优化CAR-T中的潜在作用是必要的。
Vitamin D insufficiency is a potentially modifiable risk factor for poor outcomes in newly diagnosed large B-cell lymphoma (LBCL). However, the role of circulating vitamin D concentrations in relapsed/refractory LBCL treated with CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) is currently unknown. This was a single-center, observational study that evaluated the association of pre-CAR-T 25-hydroxyvitamin D (25-OHD) status with 100-day complete response, progression-free survival, overall survival, and CAR-T related toxicity in 111 adult relapsed/refractory LBCL patients. Vitamin D insufficiency was defined as ≤30 ng/ml in accordance with the Endocrine Society guidelines. The median pre-CAR-T 25-hydroxyvitamin-D concentration was 24 ng/ml (IQR 18–34). Vitamin D insufficient patients (≤30 ng/ml; n=73 [66%]) were significantly younger than their vitamin D replete (>30 ng/ml; n=38 [34%]) counterparts (p=0.039). The vitamin D insufficient cohort was enriched for de novo LBCL as the histological subtype (p=0.026) and had a higher proportion of tisagenlecleucel as the CAR-T product (p=0.049). There were no other significant differences in the baseline characteristics between the two groups. In vitamin D insufficient compared to replete patients, 100-day complete response was 55% vs. 76% (p=0.029) and 2-year overall survival was 41% vs. 71% (p=0.061), respectively. In multivariate analysis, vitamin D insufficiency remained significantly associated with 100-day complete response (OR 2.58 [1.05–6.83]; p=0.045) and overall survival (HR 2.24 [1.08–4.66], p=0.030). In recipients of tisagenlecleucel, vitamin D insufficiency was associated with significantly lower cell viability of the infused CAR-T product (p=0.015). Finally, pretreatment vitamin D insufficiency did not predict for subsequent CAR-T related toxicity. This is the first report to demonstrate that vitamin D insufficiency is associated with inferior clinical outcomes in CAR-T recipients. Further study into the mechanistic insights of this finding, and the potential role of vitamin D supplementation to optimize CAR-T are warranted.
登录
查看更多内容
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
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：
Borchmann, Sven;Cirillo, Melita;Engert, Andreas
通讯作者：
Engert, Andreas
影响因子：
20.3
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
通讯作者：
Neelapu SS
影响因子：
3.2
作者：
Macedo R;Pasin C;Ganetsky A;Harle D;Wang XK;Belay K;Richman LP;Huffman AP;Vonderheide RH;Yates AJ;Porter DL;Wang Y;Zhang Y;Reshef R
通讯作者：
Reshef R