背景:在临床实践中使用肠胃外蛋白酶体抑制剂(PI)实现长期治疗可能具有挑战性。
目的:为了增加PI治疗的持续时间,改善结果,并保持QoL。
方法:前瞻性研究(NCT03173092)评估从基于硼替佐米的肠胃外诱导到全口服IRd的iCT。IRd接受多达39个周期或直至进展/毒性(MandaCLML2020)。先前报告了中期数据(N=101)(RifkinASH2021)。我们报告了完全累积的研究队列的结果(完成的登记,2021年5月;N=141)。
方法:美国社区网站。
方法:移植不合格/延迟移植(≥24个月)NDMM患者,疾病≥稳定,经过3个周期的硼替佐米诱导。
方法:主要终点:2年无进展生存率(PFS)。其他端点包括:关键次要,总反应率(ORR;部分反应[PR]+非常好的PR[VPGR]+完全缓解[CR])和治疗持续时间(DOT);次要,总生存期(OS),安全,和QoL。
结果:2022年2月28日,140名患者(中位年龄,72.5年[范围,48-90];79%≥65岁;42%≥75岁)已接受IRd;94%在IRd开始时具有≥1合并症。中位随访时间为20.0个月。2年PFS为69%(95%置信区间[CI]:59-77%)。ORR为62%(CR,8%;VGPR,24%;PR,30%)基于硼替佐米的诱导后,增加到78%(CR,33%;VGPR,27%;PR,18%)后iCT。在数据截止时,28名患者(20%)正在接受IRd,IRd的平均DOT为10.0个月,所有基于PI的治疗的中位持续时间为12.7个月.2年OS为85%(95%CI:76-90%)。66%的患者出现≥3级治疗紧急不良事件(TEAEs)(治疗相关,36%),44%有严重的TEAE(治疗相关,14%),并发生了6例研究中的死亡。最常见的TEAE(任何等级/≥3级)为腹泻(48%/9%),未在其他地方分类的周围神经病变(39%/4%),和疲劳(34%/4%)。修改/停药ixazomib,来那度胺,59%/15%的患者发生TEAE或地塞米松。患者报告的QoL(EORTCQLQ-C30全球健康状况/QoL评分)和治疗满意度(TSQM-9全球满意度,有效性,和便利性评分)在IRd上保持不变。
结论:在这些大多数老年人中,在iCT到IRd后观察到改善的反应和有希望的PFS和OS,社区治疗的NDMM和合并症患者,对QoL/治疗满意度无不利影响。安全性结果与以前的报告一致。
BACKGROUND: Achieving prolonged therapy with parenteral proteasome inhibitors (PIs) in clinical practice can be challenging.
OBJECTIVE: To increase the duration of PI-based therapy, improve outcomes, and maintain QoL.
METHODS: Prospective study (NCT03173092) evaluating iCT from parenteral bortezomib-based induction to all-oral IRd. IRd was received for up to 39 cycles or until progression/toxicity (Manda CLML 2020). Interim data (N=101) were previously reported (Rifkin ASH 2021). We report results from the fully accrued study cohort (enrollment completed, May 2021; N=141).
METHODS: US community sites.
METHODS: Transplant-ineligible/delayed-transplant (≥24 months) NDMM patients with ≥stable disease after 3 cycles of bortezomib-based induction.
METHODS: Primary endpoint: 2-year progression-free survival (PFS) rate. Other endpoints included: key secondary, overall response rate (ORR; partial response [PR]+very good PR [VPGR]+complete response [CR]) and duration of treatment (DOT); secondary, overall survival (OS), safety, and QoL.
RESULTS: At Feb-28-2022, 140 patients (median age, 72.5 years [range, 48-90]; 79% ≥65 years; 42% ≥75 years) had received IRd; 94% had ≥1 comorbidity at IRd initiation. Median follow-up was 20.0 months. 2-year PFS was 69% (95% confidence interval [CI]: 59-77%). ORR was 62% (CR, 8%; VGPR, 24%; PR, 30%) after bortezomib-based induction, increasing to 78% (CR, 33%; VGPR, 27%; PR, 18%) after iCT. At data cut-off, 28 patients (20%) were ongoing on IRd, median DOT with IRd was 10.0 months, and median duration of all PI-based treatment was 12.7 months. 2-year OS was 85% (95% CI: 76-90%). 66% of patients had grade ≥3 treatment-emergent adverse events (TEAEs) (treatment-related, 36%), 44% had serious TEAEs (treatment-related, 14%), and 6 on-study deaths had occurred. Most common TEAEs (any-grade/grade ≥3) were diarrhea (48%/9%), peripheral neuropathies not elsewhere classified (39%/4%), and fatigue (34%/4%). Modification/discontinuation of ixazomib, lenalidomide, or dexamethasone due to TEAEs occurred in 59%/15% of patients. Patient-reported QoL (EORTC QLQ-C30 Global Health Status/QoL score) and treatment satisfaction (TSQM-9 Global Satisfaction, Effectiveness, and Convenience scores) were maintained on IRd.
CONCLUSIONS: Improved responses and promising PFS and OS were seen following iCT to IRd in these mostly elderly, community-treated patients with NDMM and comorbidities, with no adverse impact on QoL/treatment satisfaction. Safety results were consistent with previous reports.