美国哈佛医学院Nikhil C. Munshi团队研究了Idecabtagene Vicleucel治疗复发难治性多发性骨髓瘤的疗效。2021年2月25日，该研究发表在《新英格兰医学杂志》上。

Idecabatgene-vicleucel（ide-cel，又称bb2121）是一种B细胞成熟抗原导向的嵌合抗原受体（CAR）T细胞疗法，在复发和难治性多发性骨髓瘤患者中显示出预期的CAR-T细胞毒性作用。

在这项临床2期研究中，为了证实ide-cel治疗复发和难治性骨髓瘤的有效性和安全性，研究组招募了至少接受过三种治疗方案（包括蛋白酶体抑制剂、免疫调节剂和抗CD38抗体）的患者，均接受150×10⁶至450×10⁶ CAR阳性（CAR+）T细胞的ide-cel靶剂量。主要终点为总体缓解，关键次要终点为完全缓解或更好。

140例患者中共有128例接受ide-cel治疗。在平均13.3个月的随访中，128名患者中有94名（73%）缓解，其中42名（33%）完全缓解或更好。共有33名患者（26%）的微小残留病（MRD）呈阴性状态（<10⁻⁵个有核细胞），在42名完全缓解或更好的患者中占79%。中位无进展生存期为8.8个月。

128例患者中常见的毒性反应包括中性粒细胞减少117例（91%）、贫血89例（70%）、血小板减少81例（63%）。107名患者（84%）报告了细胞因子释放综合征，其中7名（5%）患者的事件等级为3级或更高。神经毒性反应23例（18%），其中3级4例（3%），没有高于3级的神经毒性反应发生。细胞动力学分析证实49例患者中有29例（59%）在输注后6个月出现CAR+T细胞，11例患者中有4例（36%）在输注后12个月出现CAR+T细胞。

研究结果表明，在大多数难治性和复发性骨髓瘤的重度预处理患者中，Ide-cel诱导缓解；26%的治疗患者MRD阴性。几乎所有患者都有3级或4级毒性反应，最常见的是血液毒性反应和细胞因子释放综合征。

附：英文原文

Title: Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma

Author: Nikhil C. Munshi, M.D.,, Larry D. Anderson, Jr., M.D., Ph.D.,, Nina Shah, M.D.,, Deepu Madduri, M.D.,, Jesús Berdeja, M.D.,, Sagar Lonial, M.D.,, Noopur Raje, M.D.,, Yi Lin, M.D., Ph.D.,, David Siegel, M.D., Ph.D.,, Albert Oriol, M.D.,, Philippe Moreau, M.D.,, Ibrahim Yakoub-Agha, M.D., Ph.D.,, Michel Delforge, M.D.,, Michele Cavo, M.D.,, Hermann Einsele, M.D.,, Hartmut Goldschmidt, M.D.,, Katja Weisel, M.D.,, Alessandro Rambaldi, M.D.,, Donna Reece, M.D.,, Fabio Petrocca, M.D.,, Monica Massaro, M.P.H.,, Jamie N. Connarn, Ph.D.,, Shari Kaiser, Ph.D.,, Payal Patel, Ph.D.,, Liping Huang, Ph.D.,, Timothy B. Campbell, M.D., Ph.D.,, Kristen Hege, M.D.,, and Jesús San-Miguel, M.D., Ph.D.

Issue&Volume: 2021-02-24

Abstract:

Background

Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma.

Methods

In this phase 2 study, we sought to confirm the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma. Patients with disease after at least three previous regimens including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody were enrolled. Patients received ide-cel target doses of 150×106 to 450×106 CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses).

Results

Of 140 patients enrolled, 128 received ide-cel. At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. Minimal residual disease (MRD)–negative status (<105 nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion.

Conclusions

Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 toxic effects, most commonly hematologic toxic effects and cytokine release syndrome.

DOI: 10.1056/NEJMoa2024850

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2024850