来那度胺、硼替佐米和地塞米松联合依鲁替尼或伊沙妥昔单抗治疗初诊多发性骨髓瘤患者后的干细胞采集:来自 GMMG-HD6 和 -HD7 试验的单中心经验。

Stem cell collection after lenalidomide, bortezomib and dexamethasone plus elotuzumab or isatuximab in newly diagnosed multiple myeloma patients: a single centre experience from the GMMG-HD6 and -HD7 trials.

机构信息

Department of Haematology, Oncology and Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany.

出版信息

BMC Cancer. 2023 Nov 21;23(1):1132. doi: 10.1186/s12885-023-11507-9.

Abstract

BACKGROUND

While quadruplet induction therapies deepen responses in newly diagnosed multiple myeloma patients, their impact on peripheral blood stem cell (PBSC) collection remains incompletely understood. This analysis aims to evaluate the effects of prolonged lenalidomide induction and isatuximab- or elotuzumab-containing quadruplet induction therapies on PBSC mobilization and collection.

METHODS

A total of 179 transplant-eligible patients with newly diagnosed MM treated at a single academic center were included. The patients were evaluated based on PBSC mobilization and collection parameters, including overall collection results, CD34 cell levels in peripheral blood, leukapheresis (LP) delays, overall number of LP sessions, and the rate of rescue mobilization with plerixafor. The patients underwent four different induction regimens: Lenalidomide, bortezomib, and dexamethasone (RVd, six 21-day cycles, n = 44), isatuximab-RVd (six 21-day cycles, n = 35), RVd (four 21-day cycles, n = 51), or elotuzumab-RVd (four 21-day cycles, n = 49).

RESULTS

The patients' characteristics were well balanced across the different groups. Collection failures, defined as the inability to collect three sufficient PBSC transplants, were rare (n = 3, 2%), with no occurrences in the isatuximab-RVd and elotuzumab-RVd groups. Intensified induction with six 21-day cycles of RVd did not negatively impact the overall number of collected PBSCs (9.7 × 10/kg bw versus 10.5 × 10/kg bw, p = 0.331) compared to four 21-day cycles of RVd. Plerixafor usage was more common after six cycles of RVd compared to four cycles (16% versus 8%). Addition of elotuzumab to RVd did not adversely affect overall PBSC collection (10.9 × 10/kg bw versus 10.5 × 10/kg bw, p = 0.915). Patients treated with isatuximab-RVd (six cycles) had lower numbers of collected stem cells compared to those receiving RVd (six cycles) induction (8.8 × 10/kg bw versus 9.7 × 10/kg bw, p = 0.801), without experiencing significant delays in LP or increased numbers of LP sessions in a multivariable logistic regression analysis. Plerixafor usage was more common after isatuximab plus RVd compared to RVd alone (34% versus 16%).

CONCLUSIONS

This study demonstrates that stem cell collection is feasible after prolonged induction with isatuximab-RVd without collection failures and might be further explored as induction therapy.

TRIAL REGISTRATION

Patients were treated within the randomized phase III clinical trials GMMG-HD6 (NCT02495922, 24/06/2015) and GMMG-HD7 (NCT03617731, 24/07/2018). However, during stem cell mobilization and -collection, no study-specific therapeutic intervention was performed.

摘要

背景

虽然四联诱导疗法可加深新诊断多发性骨髓瘤患者的应答,但对外周血造血干细胞(PBSC)采集的影响仍不完全清楚。本分析旨在评估延长来那度胺诱导的效果以及包含伊沙妥昔单抗或埃罗妥珠单抗的四联诱导疗法对 PBSC 动员和采集的影响。

方法

共纳入了在单一学术中心接受治疗的 179 例有移植资格的新发 MM 患者。根据 PBSC 动员和采集参数评估患者,包括总体采集结果、外周血中 CD34 细胞水平、白细胞单采(LP)延迟、总 LP 次数以及使用普乐沙福进行挽救性动员的比例。患者接受了四种不同的诱导方案:来那度胺、硼替佐米和地塞米松(RVd,6 个 21 天周期,n=44)、伊沙妥昔单抗-RVd(6 个 21 天周期,n=35)、RVd(4 个 21 天周期,n=51)或埃罗妥珠单抗-RVd(4 个 21 天周期,n=49)。

结果

不同组之间患者的特征均衡。采集失败(定义为无法采集到三个足够的 PBSC 移植)的情况很少见(n=3,2%),在伊沙妥昔单抗-RVd 和埃罗妥珠单抗-RVd 组中均未发生。与 4 个 21 天周期的 RVd 相比,6 个 21 天周期的 RVd 强化诱导不会对总体采集的 PBSC 数量产生负面影响(9.7×10/kg bw 与 10.5×10/kg bw,p=0.331)。与 4 个 21 天周期的 RVd 相比,使用普乐沙福的情况在 6 个周期的 RVd 后更为常见(16%与 8%)。在 RVd 中加入埃罗妥珠单抗并不会对总体 PBSC 采集产生不利影响(10.9×10/kg bw 与 10.5×10/kg bw,p=0.915)。与接受 RVd(6 个周期)诱导的患者相比,接受伊沙妥昔单抗-RVd(6 个周期)治疗的患者采集的干细胞数量更少(8.8×10/kg bw 与 9.7×10/kg bw,p=0.801),但 LP 延迟或 LP 次数增加在多变量逻辑回归分析中并不显著。与 RVd 相比,伊沙妥昔单抗加 RVd 后使用普乐沙福的情况更为常见(34%与 16%)。

结论

本研究表明,在伊沙妥昔单抗-RVd 延长诱导后,干细胞采集是可行的,不会出现采集失败,可能作为诱导治疗进一步探索。

试验注册

患者在随机 III 期临床试验 GMMG-HD6(NCT02495922,24/06/2015)和 GMMG-HD7(NCT03617731,24/07/2018)中接受治疗。然而,在干细胞动员和采集期间,没有进行任何特定于研究的治疗干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60f/10664363/8ea3e678e4cb/12885_2023_11507_Fig1_HTML.jpg

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