自体抗 BCMA 嵌合抗原受体 T 细胞（liso-cel）治疗二线弥漫大 B 细胞淋巴瘤（DLBCL）的 3 期 TRANSFORM 研究的主要分析结果

Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study.

机构信息

Massachusetts General Hospital Cancer Center, Harvard Medical School, Harvard University, Boston, MA.

Transplant and Cellular Immunotherapy Program, Northside Hospital Cancer Institute, Atlanta, GA.

出版信息

Blood. 2023 Apr 6;141(14):1675-1684. doi: 10.1182/blood.2022018730.

DOI:10.1182/blood.2022018730

PMID:36542826

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10646768/

Abstract

This global phase 3 study compared lisocabtagene maraleucel (liso-cel) with a standard of care (SOC) as second-line therapy for primary refractory or early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (ASCT; N = 184) were randomly assigned in a 1:1 ratio to liso-cel (100 × 106 chimeric antigen receptor-positive T cells) or SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose chemotherapy and ASCT in responders). The primary end point was event-free survival (EFS). In this primary analysis with a 17.5-month median follow-up, median EFS was not reached (NR) for liso-cel vs 2.4 months for SOC. Complete response (CR) rate was 74% for liso-cel vs 43% for SOC (P < .0001) and median progression-free survival (PFS) was NR for liso-cel vs 6.2 months for SOC (hazard ratio [HR] = 0.400; P < .0001). Median overall survival (OS) was NR for liso-cel vs 29.9 months for SOC (HR = 0.724; P = .0987). When adjusted for crossover from SOC to liso-cel, 18-month OS rates were 73% for liso-cel and 54% for SOC (HR = 0.415). Grade 3 cytokine release syndrome and neurological events occurred in 1% and 4% of patients in the liso-cel arm, respectively (no grade 4 or 5 events). These data show significant improvements in EFS, CR rate, and PFS for liso-cel compared with SOC and support liso-cel as a preferred second-line treatment compared with SOC in patients with primary refractory or early relapsed LBCL. This trial was registered at www.clinicaltrials.gov as #NCT03575351.

摘要

这项全球性的 3 期研究比较了 lisocabtagene maraleucel（liso-cel）与标准治疗（SOC）作为原发性难治性或早期复发（≤12 个月）大 B 细胞淋巴瘤（LBCL）的二线治疗。符合自体干细胞移植（ASCT；N = 184）条件的成年人以 1:1 的比例随机分配接受 liso-cel（100×106 个嵌合抗原受体阳性 T 细胞）或 SOC（3 个周期的铂类免疫化疗，随后在应答者中进行高剂量化疗和 ASCT）。主要终点是无事件生存（EFS）。在中位随访 17.5 个月的主要分析中，liso-cel 的中位 EFS未达到（NR），而 SOC 为 2.4 个月。liso-cel 的完全缓解（CR）率为 74%，SOC 为 43%（P<.0001），中位无进展生存（PFS）NR 为 liso-cel，SOC 为 6.2 个月（HR=0.400；P<.0001）。liso-cel 的中位总生存（OS）NR 为 SOC 为 29.9 个月（HR=0.724；P=0.0987）。当调整 SOC 交叉至 liso-cel 后，liso-cel 的 18 个月 OS 率为 73%，SOC 为 54%（HR=0.415）。liso-cel 组分别有 1%和 4%的患者发生 3 级细胞因子释放综合征和神经系统事件（无 4 级或 5 级事件）。这些数据表明，与 SOC 相比，liso-cel 在 EFS、CR 率和 PFS 方面有显著改善，支持 liso-cel 作为原发性难治性或早期复发 LBCL 患者的二线首选治疗。该试验在 www.clinicaltrials.gov 上注册为#NCT03575351。