Clinical responses and pharmacokinetics of fully human BCMA targeting CAR T-cell therapy in relapsed/refractory multiple myeloma
| العنوان: | Clinical responses and pharmacokinetics of fully human BCMA targeting CAR T-cell therapy in relapsed/refractory multiple myeloma |
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| المؤلفون: | Guang Hu, Jianfeng Zhou, Xia Mao, Aihua Du, Chunrui Li, Li Meng, Xiaoxi Zhou, Liting Chen, Zhenya Hong, Jue Wang |
| المصدر: | Journal of Clinical Oncology. 37:8013-8013 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, business.industry, Refractory Multiple Myeloma, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, 030220 oncology & carcinogenesis, Internal medicine, Relapsed refractory, Medicine, CAR T-cell therapy, business, Multiple myeloma, 030215 immunology |
| الوصف: | 8013 Background: Previous studies indicate patients with relapsed/refractory multiple myeloma (RRMM) who receive high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells is not effective. To solve this dilemma, we have developed a novel BCMA-targeting CAR-T (CT103A) with a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3z activation domains. Methods: ChiCTR1800018137 is a single-center and single-arm trial of CT103A in patients with RRMM. The primary objectives are to characterize the safety and tolerability in patients with R/R MM. The secondary objectives include evaluation of anti-myeloma activity, cytokines, CAR-T cell persistence, and pharmacokinetics. Between September 21, 2018, and January 21, 2019, nine patients (including 3 patients having relapsed after being given a murine BCMA CAR-T) received CT103A in 3+3 dose-escalation trial (three doses at 1, 3, 6 ×106/kg) after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. All Patients had received a median of 4 prior lines (range 3 - 5) of MM therapy. Results: At the time of the February 4, 2019 data analysis, the overall response rate was 100% (Table), and all patients had a rapid response within 14 days, with 67% (2/3) reaching CR/sCR at the lowest dose. The pharmacokinetics of CT103A were assessed by a digital polymerase chain reaction. Robust expansions were seen even at the lowest dosage level. In addition, Cmax and AUC0-28 reached levels comparable to reported CD19 CAR-T. In the first two dose groups, the grade of cytokine release syndrome (CRS) was 0 - 2. In the 6 ×106 /kg dose group, DLT had been observed in one patient. Conclusions: Data from this early-stage clinical study showed the unparalleled safety and efficacy of CT103A. Major AEs were transient, manageable, and reversible. three patients who relapsed the murine BCMA CAR-T were treated with CT103A, two patients achieved CR, and one patient achieved VGPR. 100% ORR and a rapid response within 2 weeks, suggests CT103A could be developed as a competitive therapeutic to treat patients with RRMM. Treatment Response (Case 1,5 and 7 are patients who relapsed the murine BCMA CAR-T). Clinical trial information: ChiCTR1800018137. [Table: see text] |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::57332078af1c80b307ff892f0e3ce4f1Test https://doi.org/10.1200/jco.2019.37.15_suppl.8013Test |
| رقم الانضمام: | edsair.doi...........57332078af1c80b307ff892f0e3ce4f1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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