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达雷妥尤单抗(Dara)和来那度胺(Len)联合四联诱导疗法用于新诊断多发性骨髓瘤(NDMM)患者的干细胞动员效果:两家机构的真实世界经验

Stem Cell Mobilization Yields with Daratumumab (Dara) and Lenalidomide (Len)-Containing Quadruplet Induction Therapy in Patients with Newly Diagnosed Multiple Myeloma (NDMM): A Real-World Experience at 2 Institutes.

作者信息

Varga Cindy, Robinson Myra, Gupta Vikas, Hofmeister Craig C, Nooka Ajay K, Kaufman Jonathan L, Dhodapkar Madhav V, Lonial Sagar, Borden Shanice, Ferreri Christopher, Paul Barry, Atrash Shebli, Bhutani Manisha, Voorhees Peter M, Joseph Nisha S

机构信息

Atrium Health Wake Forest University School of Medicine, Levine Cancer Institute, Charlotte, NC.

Department of Biostatistics and Data Sciences, Levine Cancer Institute, Charlotte, NC.

出版信息

Clin Lymphoma Myeloma Leuk. 2025 Aug;25(8):e563-e569. doi: 10.1016/j.clml.2025.04.003. Epub 2025 Apr 11.

Abstract

BACKGROUND

Quadruplet therapy has become standard frontline therapy in transplant eligible NDMM patients. Using data from the MASTER and GRIFFIN trials, Chhabra et al. reported that Dara-Len containing quadruplet therapies had minimal impact on stem cell harvesting and engraftment. It is unclear if this remains true in a real-world setting where heterogeneity exists among patients and in institutional practices. Herein, we describe our experience of stem cell mobilization and collection in NDMM patients receiving DRVd at Levine Cancer Institute (LCI) and Emory Winship Cancer Institute.

METHODS

In this multi-center retrospective analysis, NDMM patients were eligible if they received DRVd and pursued stem cell collection between September, 2019 and January, 2024 at LCI and January, 2019 and July, 2022 at Emory. Patients either received 10 mcg/kg of growth colony-stimulating factor (G-CSF) daily (LCI) or 7.5 mcg/kg twice daily (Emory) for 4 days prior to collection and 1 dose on the morning of apheresis. Plerixafor was provided on day -1 of apheresis as a preemptive mobilization strategy at LCI and on an as needed basis at Emory. Patients with a suboptimal stem cell yield on day 1 received additional doses of G-CSF with or without rescue plerixafor at both sites followed by a second day of stem cell collection. Stem cell yield failure was defined as the inability to achieve a minimal goal dose of 2.0 × 10 cells/kg. Categorical outcomes were summarized with frequencies and proportions while numerical outcomes were summarized with descriptive statistics. Select data elements were only available in the LCI cohort.

RESULTS

A total of 423 patients were analyzed. The median patient age was 62 years (range, 23-79), and 38.1% of the cohort was African American. Thirteen percent of the cohort had high risk cytogenetics and 19.1% had ISS stage III disease. At LCI, patients received a median of 4 (range, 1-14) cycles of induction therapy before stem cell collection. In the entire cohort, 88.8% of patients received 21-day cycles and 11.2% received 28-day cycles. Most patients achieved a VGPR or better (87.2%) after induction and, of those with MRD data available at LCI, 41.6% (37 of 89) achieved MRD negative status (at 10). Of those with available data (n = 92), stem cell collection occurred after a median of 4 weeks (range, 2 to 8) from induction completion. All patients at LCI and 308 of the 318 (96.9%) patients at Emory received plerixafor. Among the entire cohort, the median number of total CD34+ cells collected was 9.0 × 10 CD34+ cells/kg (range 0-24.1). By institute, the median number of CD34+ cells across all attempts at LCI was 8.5 × 10 CD34+ cells/kg (range 2.9-18.1) and the median at Emory was 9.0 × 10 CD34+ cells/kg (0-24.1) indicating that there was no significant difference between mobilization strategies (P = .088). There also was no significant difference in stem cell yield between the 21-day and 28-day cycles; median yield was 9.0 × 10 CD34+ cells/kg versus 8.6 × 10 CD34+ cells/kg, respectively (P = .246). About 94.3% (N = 397) of patients collected enough for 2 transplants. Only 2.8% (12 of 423) required an additional mobilization attempt to achieve the minimal target stem cell yield. In the entire population, there was 1 mobilization failure (0.2%) and all but 1 patient who required remobilization collected sufficient stem cells.

CONCLUSION

The addition of Dara to RVd induction therapy led to impressive hematologic responses and did not have a deleterious effect on stem cell mobilization with an upfront plerixafor strategy. The median stem cell yield in this real-world experience was slightly better than that reported in the GRIFFIN trial.

摘要

背景

四联疗法已成为适合移植的新诊断多发性骨髓瘤(NDMM)患者的标准一线治疗方案。Chhabra等人利用MASTER和GRIFFIN试验的数据报告称,含达雷妥尤单抗(Dara)和来那度胺(Len)的四联疗法对干细胞采集和植入的影响最小。在患者存在异质性且机构实践各异的现实环境中,情况是否依然如此尚不清楚。在此,我们描述了在莱文癌症研究所(LCI)和埃默里温希普癌症研究所接受达雷妥尤单抗联合硼替佐米、来那度胺和地塞米松(DRVd)方案治疗的NDMM患者的干细胞动员和采集经验。

方法

在这项多中心回顾性分析中,NDMM患者若在2019年9月至2024年1月于LCI以及2019年1月至2022年7月于埃默里接受DRVd方案治疗并进行干细胞采集,则符合入选标准。患者在采集前4天每天接受10 mcg/kg的粒细胞集落刺激因子(G-CSF)(LCI)或每天两次、每次7.5 mcg/kg(埃默里),并在采集日上午额外接受1剂。在LCI,在采集日-1给予普乐沙福作为预先动员策略,在埃默里则根据需要给予。第1天干细胞产量未达最佳的患者在两个中心均接受额外剂量的G-CSF,可联合或不联合挽救性普乐沙福,随后进行第二天的干细胞采集。干细胞产量失败定义为无法达到最低目标剂量2.0×10⁶细胞/kg。分类结果用频率和比例进行总结,数值结果用描述性统计进行总结。部分数据元素仅在LCI队列中可用。

结果

共分析了423例患者。患者中位年龄为62岁(范围23 - 79岁),队列中38.1%为非裔美国人。13%的队列患者具有高危细胞遗传学特征,19.1%患有国际分期系统(ISS)III期疾病。在LCI中心,患者在干细胞采集前接受诱导治疗的中位周期数为4个(范围1 - 14个)。在整个队列中,88.8%的患者接受21天周期治疗,11.2%接受28天周期治疗。大多数患者诱导治疗后达到非常好的部分缓解(VGPR)或更好(87.2%),在LCI有可获得微小残留病(MRD)数据的患者中,41.6%(89例中的37例)达到MRD阴性状态(10⁻⁵)。在有可用数据的患者中(n = 92),干细胞采集在诱导完成后中位4周(范围2至8周)进行。LCI的所有患者以及埃默里318例患者中的308例(96.9%)接受了普乐沙福。在整个队列中,采集的总CD34⁺细胞中位数量为9.0×10⁶ CD34⁺细胞/kg(范围0 - 24.1)。按中心来看,LCI所有采集尝试中CD34⁺细胞的中位数量为8.5×10⁶ CD34⁺细胞/kg(范围2.9 - 18.1),埃默里为9.0×10⁶ CD34⁺细胞/kg(0 - 24.1),表明动员策略之间无显著差异(P = .088)。21天和28天周期的干细胞产量也无显著差异;中位产量分别为9.0×10⁶ CD34⁺细胞/kg和8.6×10⁶ CD34⁺细胞/kg(P = .246)。约94.3%(N = 397)的患者采集的细胞量足够进行2次移植。仅2.8%(423例中的12例)患者需要额外进行一次动员尝试以达到最低目标干细胞产量。在整个人群中,有1例动员失败(0.2%),除1例需要再次动员的患者外,其他患者均采集到了足够的干细胞。

结论

在RVd诱导治疗中加入达雷妥尤单抗可带来显著的血液学反应,并且采用预先使用普乐沙福的策略对干细胞动员没有有害影响。在这一现实世界经验中,干细胞中位产量略优于GRIFFIN试验报告的结果。

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