Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma : a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2)
© 2022. The Author(s)..
BACKGROUND: LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years.
METHODS: LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 106 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy.
RESULTS: As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer.
CONCLUSIONS: The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Journal of hematology & oncology - 15(2022), 1 vom: 06. Juli, Seite 86 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhao, Wan-Hong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.07.2022 Date Revised 27.07.2022 published: Electronic ClinicalTrials.gov: NCT03090659 Citation Status MEDLINE |
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| doi: |
10.1186/s13045-022-01301-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM343152339 |
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| 100 | 1 | |a Zhao, Wan-Hong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma |b a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2) |
| 264 | 1 | |c 2022 | |
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| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 08.07.2022 | ||
| 500 | |a Date Revised 27.07.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03090659 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a BACKGROUND: LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years | ||
| 520 | |a METHODS: LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 106 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy | ||
| 520 | |a RESULTS: As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer | ||
| 520 | |a CONCLUSIONS: The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285 | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a B cell maturation antigen | |
| 650 | 4 | |a Chimeric antigen receptor therapy | |
| 650 | 4 | |a Efficacy | |
| 650 | 4 | |a Multiple myeloma | |
| 650 | 4 | |a Safety | |
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| 650 | 7 | |a Cyclophosphamide |2 NLM | |
| 650 | 7 | |a 8N3DW7272P |2 NLM | |
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| 700 | 1 | |a Chen, Li-Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Wei-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Shi-Wei |e verfasserin |4 aut | |
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| 700 | 1 | |a Cao, Xing-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yi-Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Fang-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Peng-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Lei, Bo |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Liu-Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jian-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Ju |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Han |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Xiao-Hu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jian-Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wang-Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Mi, Jian-Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Sai-Juan |e verfasserin |4 aut | |
| 700 | 1 | |a He, Ai-Li |e verfasserin |4 aut | |
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