Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study
Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Met...
Ausführliche Beschreibung
Autor*in: |
Pan, Jing [verfasserIn] Tang, Kaiting [verfasserIn] Luo, Yuechen [verfasserIn] Seery, Samuel [verfasserIn] Tan, Yue [verfasserIn] Deng, Biping [verfasserIn] Liu, Feng [verfasserIn] Xu, Xiuwen [verfasserIn] Ling, Zhuojun [verfasserIn] Song, Weiliang [verfasserIn] Xu, Jinlong [verfasserIn] Duan, Jiajia [verfasserIn] Wang, Zelin [verfasserIn] Li, Chunyu [verfasserIn] Wang, Kai [verfasserIn] Zhang, Yibing [verfasserIn] Yu, Xinjian [verfasserIn] Zheng, Qinlong [verfasserIn] Zhao, Liping [verfasserIn] Zhang, Jiecheng [verfasserIn] Chang, Alex H [verfasserIn] Feng, Xiaoming [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2023 |
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Übergeordnetes Werk: |
Enthalten in: The lancet |
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Übergeordnetes Werk: |
volume:24 ; pages:1229-1241 |
DOI / URN: |
10.1016/S1470-2045(23)00436-9 |
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Katalog-ID: |
ELV065386523 |
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245 | 1 | 0 | |a Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study |
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520 | |a Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia.Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences.Translation: For the Chinese translation of the abstract see Supplementary Materials section. | ||
700 | 1 | |a Tang, Kaiting |e verfasserin |4 aut | |
700 | 1 | |a Luo, Yuechen |e verfasserin |4 aut | |
700 | 1 | |a Seery, Samuel |e verfasserin |4 aut | |
700 | 1 | |a Tan, Yue |e verfasserin |4 aut | |
700 | 1 | |a Deng, Biping |e verfasserin |4 aut | |
700 | 1 | |a Liu, Feng |e verfasserin |4 aut | |
700 | 1 | |a Xu, Xiuwen |e verfasserin |4 aut | |
700 | 1 | |a Ling, Zhuojun |e verfasserin |4 aut | |
700 | 1 | |a Song, Weiliang |e verfasserin |4 aut | |
700 | 1 | |a Xu, Jinlong |e verfasserin |4 aut | |
700 | 1 | |a Duan, Jiajia |e verfasserin |4 aut | |
700 | 1 | |a Wang, Zelin |e verfasserin |4 aut | |
700 | 1 | |a Li, Chunyu |e verfasserin |4 aut | |
700 | 1 | |a Wang, Kai |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Yibing |e verfasserin |4 aut | |
700 | 1 | |a Yu, Xinjian |e verfasserin |4 aut | |
700 | 1 | |a Zheng, Qinlong |e verfasserin |4 aut | |
700 | 1 | |a Zhao, Liping |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Jiecheng |e verfasserin |4 aut | |
700 | 1 | |a Chang, Alex H |e verfasserin |4 aut | |
700 | 1 | |a Feng, Xiaoming |e verfasserin |4 aut | |
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10.1016/S1470-2045(23)00436-9 doi (DE-627)ELV065386523 (ELSEVIER)S1470-2045(23)00436-9 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Pan, Jing verfasserin aut Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia.Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences.Translation: For the Chinese translation of the abstract see Supplementary Materials section. Tang, Kaiting verfasserin aut Luo, Yuechen verfasserin aut Seery, Samuel verfasserin aut Tan, Yue verfasserin aut Deng, Biping verfasserin aut Liu, Feng verfasserin aut Xu, Xiuwen verfasserin aut Ling, Zhuojun verfasserin aut Song, Weiliang verfasserin aut Xu, Jinlong verfasserin aut Duan, Jiajia verfasserin aut Wang, Zelin verfasserin aut Li, Chunyu verfasserin aut Wang, Kai verfasserin aut Zhang, Yibing verfasserin aut Yu, Xinjian verfasserin aut Zheng, Qinlong verfasserin aut Zhao, Liping verfasserin aut Zhang, Jiecheng verfasserin aut Chang, Alex H verfasserin aut Feng, Xiaoming verfasserin aut Enthalten in The lancet <London> / Oncology London : The Lancet Publ. Group, 2000 24, Seite 1229-1241 Online-Ressource (DE-627)325349770 (DE-600)2035574-9 (DE-576)100517544 1474-5488 nnns volume:24 pages:1229-1241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 24 1229-1241 |
spelling |
10.1016/S1470-2045(23)00436-9 doi (DE-627)ELV065386523 (ELSEVIER)S1470-2045(23)00436-9 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Pan, Jing verfasserin aut Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia.Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences.Translation: For the Chinese translation of the abstract see Supplementary Materials section. Tang, Kaiting verfasserin aut Luo, Yuechen verfasserin aut Seery, Samuel verfasserin aut Tan, Yue verfasserin aut Deng, Biping verfasserin aut Liu, Feng verfasserin aut Xu, Xiuwen verfasserin aut Ling, Zhuojun verfasserin aut Song, Weiliang verfasserin aut Xu, Jinlong verfasserin aut Duan, Jiajia verfasserin aut Wang, Zelin verfasserin aut Li, Chunyu verfasserin aut Wang, Kai verfasserin aut Zhang, Yibing verfasserin aut Yu, Xinjian verfasserin aut Zheng, Qinlong verfasserin aut Zhao, Liping verfasserin aut Zhang, Jiecheng verfasserin aut Chang, Alex H verfasserin aut Feng, Xiaoming verfasserin aut Enthalten in The lancet <London> / Oncology London : The Lancet Publ. Group, 2000 24, Seite 1229-1241 Online-Ressource (DE-627)325349770 (DE-600)2035574-9 (DE-576)100517544 1474-5488 nnns volume:24 pages:1229-1241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 24 1229-1241 |
allfields_unstemmed |
10.1016/S1470-2045(23)00436-9 doi (DE-627)ELV065386523 (ELSEVIER)S1470-2045(23)00436-9 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Pan, Jing verfasserin aut Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia.Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences.Translation: For the Chinese translation of the abstract see Supplementary Materials section. Tang, Kaiting verfasserin aut Luo, Yuechen verfasserin aut Seery, Samuel verfasserin aut Tan, Yue verfasserin aut Deng, Biping verfasserin aut Liu, Feng verfasserin aut Xu, Xiuwen verfasserin aut Ling, Zhuojun verfasserin aut Song, Weiliang verfasserin aut Xu, Jinlong verfasserin aut Duan, Jiajia verfasserin aut Wang, Zelin verfasserin aut Li, Chunyu verfasserin aut Wang, Kai verfasserin aut Zhang, Yibing verfasserin aut Yu, Xinjian verfasserin aut Zheng, Qinlong verfasserin aut Zhao, Liping verfasserin aut Zhang, Jiecheng verfasserin aut Chang, Alex H verfasserin aut Feng, Xiaoming verfasserin aut Enthalten in The lancet <London> / Oncology London : The Lancet Publ. Group, 2000 24, Seite 1229-1241 Online-Ressource (DE-627)325349770 (DE-600)2035574-9 (DE-576)100517544 1474-5488 nnns volume:24 pages:1229-1241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 24 1229-1241 |
allfieldsGer |
10.1016/S1470-2045(23)00436-9 doi (DE-627)ELV065386523 (ELSEVIER)S1470-2045(23)00436-9 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Pan, Jing verfasserin aut Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia.Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences.Translation: For the Chinese translation of the abstract see Supplementary Materials section. Tang, Kaiting verfasserin aut Luo, Yuechen verfasserin aut Seery, Samuel verfasserin aut Tan, Yue verfasserin aut Deng, Biping verfasserin aut Liu, Feng verfasserin aut Xu, Xiuwen verfasserin aut Ling, Zhuojun verfasserin aut Song, Weiliang verfasserin aut Xu, Jinlong verfasserin aut Duan, Jiajia verfasserin aut Wang, Zelin verfasserin aut Li, Chunyu verfasserin aut Wang, Kai verfasserin aut Zhang, Yibing verfasserin aut Yu, Xinjian verfasserin aut Zheng, Qinlong verfasserin aut Zhao, Liping verfasserin aut Zhang, Jiecheng verfasserin aut Chang, Alex H verfasserin aut Feng, Xiaoming verfasserin aut Enthalten in The lancet <London> / Oncology London : The Lancet Publ. Group, 2000 24, Seite 1229-1241 Online-Ressource (DE-627)325349770 (DE-600)2035574-9 (DE-576)100517544 1474-5488 nnns volume:24 pages:1229-1241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 24 1229-1241 |
allfieldsSound |
10.1016/S1470-2045(23)00436-9 doi (DE-627)ELV065386523 (ELSEVIER)S1470-2045(23)00436-9 DE-627 ger DE-627 rda eng 610 VZ 44.81 bkl Pan, Jing verfasserin aut Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia.Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences.Translation: For the Chinese translation of the abstract see Supplementary Materials section. Tang, Kaiting verfasserin aut Luo, Yuechen verfasserin aut Seery, Samuel verfasserin aut Tan, Yue verfasserin aut Deng, Biping verfasserin aut Liu, Feng verfasserin aut Xu, Xiuwen verfasserin aut Ling, Zhuojun verfasserin aut Song, Weiliang verfasserin aut Xu, Jinlong verfasserin aut Duan, Jiajia verfasserin aut Wang, Zelin verfasserin aut Li, Chunyu verfasserin aut Wang, Kai verfasserin aut Zhang, Yibing verfasserin aut Yu, Xinjian verfasserin aut Zheng, Qinlong verfasserin aut Zhao, Liping verfasserin aut Zhang, Jiecheng verfasserin aut Chang, Alex H verfasserin aut Feng, Xiaoming verfasserin aut Enthalten in The lancet <London> / Oncology London : The Lancet Publ. Group, 2000 24, Seite 1229-1241 Online-Ressource (DE-627)325349770 (DE-600)2035574-9 (DE-576)100517544 1474-5488 nnns volume:24 pages:1229-1241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_213 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2424 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.81 Onkologie VZ AR 24 1229-1241 |
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Pan, Jing @@aut@@ Tang, Kaiting @@aut@@ Luo, Yuechen @@aut@@ Seery, Samuel @@aut@@ Tan, Yue @@aut@@ Deng, Biping @@aut@@ Liu, Feng @@aut@@ Xu, Xiuwen @@aut@@ Ling, Zhuojun @@aut@@ Song, Weiliang @@aut@@ Xu, Jinlong @@aut@@ Duan, Jiajia @@aut@@ Wang, Zelin @@aut@@ Li, Chunyu @@aut@@ Wang, Kai @@aut@@ Zhang, Yibing @@aut@@ Yu, Xinjian @@aut@@ Zheng, Qinlong @@aut@@ Zhao, Liping @@aut@@ Zhang, Jiecheng @@aut@@ Chang, Alex H @@aut@@ Feng, Xiaoming @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">ELV065386523</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20231102093203.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">231102s2023 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/S1470-2045(23)00436-9</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV065386523</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S1470-2045(23)00436-9</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.81</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Pan, Jing</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. 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Pan, Jing |
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Pan, Jing ddc 610 bkl 44.81 Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study |
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610 VZ 44.81 bkl Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study |
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Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study |
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Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study |
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Pan, Jing Tang, Kaiting Luo, Yuechen Seery, Samuel Tan, Yue Deng, Biping Liu, Feng Xu, Xiuwen Ling, Zhuojun Song, Weiliang Xu, Jinlong Duan, Jiajia Wang, Zelin Li, Chunyu Wang, Kai Zhang, Yibing Yu, Xinjian Zheng, Qinlong Zhao, Liping Zhang, Jiecheng Chang, Alex H Feng, Xiaoming |
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sequential cd19 and cd22 chimeric antigen receptor t-cell therapy for childhood refractory or relapsed b-cell acute lymphocytic leukaemia: a single-arm, phase 2 study |
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Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study |
abstract |
Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia.Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences.Translation: For the Chinese translation of the abstract see Supplementary Materials section. |
abstractGer |
Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia.Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences.Translation: For the Chinese translation of the abstract see Supplementary Materials section. |
abstract_unstemmed |
Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia.Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences.Translation: For the Chinese translation of the abstract see Supplementary Materials section. |
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title_short |
Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study |
remote_bool |
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author2 |
Tang, Kaiting Luo, Yuechen Seery, Samuel Tan, Yue Deng, Biping Liu, Feng Xu, Xiuwen Ling, Zhuojun Song, Weiliang Xu, Jinlong Duan, Jiajia Wang, Zelin Li, Chunyu Wang, Kai Zhang, Yibing Yu, Xinjian Zheng, Qinlong Zhao, Liping Zhang, Jiecheng Chang, Alex H Feng, Xiaoming |
author2Str |
Tang, Kaiting Luo, Yuechen Seery, Samuel Tan, Yue Deng, Biping Liu, Feng Xu, Xiuwen Ling, Zhuojun Song, Weiliang Xu, Jinlong Duan, Jiajia Wang, Zelin Li, Chunyu Wang, Kai Zhang, Yibing Yu, Xinjian Zheng, Qinlong Zhao, Liping Zhang, Jiecheng Chang, Alex H Feng, Xiaoming |
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doi_str |
10.1016/S1470-2045(23)00436-9 |
up_date |
2024-07-06T22:51:12.913Z |
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We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments.Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1–18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 106 to 5·0 × 106 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended.Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6–10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), with a median interval of 39 days (37–41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89–100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4–20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66–91), duration of remission was 80% (68–92), and disease-free survival was 80% (68–92) with transplantation censoring; overall survival was 96% (91–100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7–14) after CD19-directed and 12 days (10–15) after CD22-directed CAR T-cell infusion. 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score |
7.3978424 |