Department of Medicine III - Hematology/Oncology, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany.
Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany.
J Hematol Oncol. 2023 Jul 31;16(1):88. doi: 10.1186/s13045-023-01465-x.
BCMA-directed CAR T-cell therapy (CAR-T) has altered the treatment landscape of relapsed/refractory (r/r) multiple myeloma, but is hampered by unique side effects that can lengthen hospital stays and increase morbidity. Hematological toxicity (e.g. profound and prolonged cytopenias) represents the most common grade ≥ 3 toxicity and can predispose for severe infectious complications. Here, we examined the utility of the CAR-HEMATOTOX (HT) score to predict toxicity and survival outcomes in patients receiving standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel.
Data were retrospectively collected from 113 r/r multiple myeloma patients treated between April 2021 and July 2022 across six international CAR-T centers. The HT score-composed of factors related to hematopoietic reserve and baseline inflammatory state-was determined prior to lymphodepleting chemotherapy.
At lymphodepletion, 63 patients were HT (score 0-1) and 50 patients were HT (score ≥ 2). Compared to their HT counterparts, HT patients displayed prolonged severe neutropenia (median 9 vs. 3 days, p < 0.001), an increased severe infection rate (40% vs. 5%, p < 0.001), and more severe ICANS (grade ≥ 3: 16% vs. 0%, p < 0.001). One-year non-relapse mortality was higher in the HT group (13% vs. 2%, p = 0.019) and was predominantly attributable to fatal infections. Response rates according to IMWG criteria were higher in HT patients (≥ VGPR: 70% vs. 44%, p = 0.01). Conversely, HT patients exhibited inferior progression-free (median 5 vs. 15 months, p < 0.001) and overall survival (median 10.5 months vs. not reached, p < 0.001).
These data highlight the prognostic utility of the CAR-HEMATOTOX score for both toxicity and treatment response in multiple myeloma patients receiving BCMA-directed CAR-T. The score may guide toxicity management (e.g. anti-infective prophylaxis, early G-CSF, stem cell boost) and help to identify suitable CAR-T candidates.
BCMA 导向的 CAR-T 细胞疗法（CAR-T）改变了复发/难治性（r/r）多发性骨髓瘤的治疗格局，但受到独特的副作用的限制，这些副作用会延长住院时间并增加发病率。血液学毒性（例如严重且持久的细胞减少症）是最常见的≥3 级毒性，可导致严重的感染并发症。在这里，我们研究了 CAR-HEMATOTOX（HT）评分在接受标准护理 idecabtagene vicleucel 和 ciltacabtagene autoleucel 的 r/r 多发性骨髓瘤患者中的预测毒性和生存结局的效用。
数据来自 2021 年 4 月至 2022 年 7 月在六个国际 CAR-T 中心接受治疗的 113 名 r/r 多发性骨髓瘤患者的回顾性收集。HT 评分由与造血储备和基线炎症状态相关的因素组成，在淋巴细胞耗竭化疗前确定。
在淋巴细胞耗竭时，63 名患者为 HT（评分 0-1），50 名患者为 HT（评分≥2）。与 HT 患者相比，HT 患者表现出延长的严重中性粒细胞减少症（中位数 9 天 vs. 3 天，p<0.001）、严重感染率增加（40% vs. 5%，p<0.001）和更严重的 ICANS（等级≥3：16% vs. 0%，p<0.001）。HT 组一年非复发死亡率更高（13% vs. 2%，p=0.019），主要归因于致命感染。根据 IMWG 标准，HT 患者的缓解率更高（≥VGPR：70% vs. 44%，p=0.01）。相反，HT 患者的无进展生存期（中位数 5 个月 vs. 15 个月，p<0.001）和总生存期（中位数 10.5 个月 vs. 未达到，p<0.001）更差。
这些数据突出了 CAR-HEMATOTOX 评分在接受 BCMA 定向 CAR-T 的多发性骨髓瘤患者中预测毒性和治疗反应的预后效用。该评分可指导毒性管理（例如抗感染预防、早期 G-CSF、干细胞助推）并帮助识别合适的 CAR-T 候选者。
