Kesavan Murali, Meyrick Danielle, Gallyamov Marat, Turner J Harvey, Yeo Sharon, Cardaci Giuseppe, Lenzo Nat P
Department of Haematology, School of Medicine, The University of Western Australia, Perth 6009, Australia.
Department of Nuclear Medicine, School of Medicine, The University of Western Australia, Perth 6009, Australia.
Diagnostics (Basel). 2021 Mar 14;11(3):515. doi: 10.3390/diagnostics11030515.
Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative Lu-DOTAGA-(I-y)fk(Sub-KuE) (Lu-PSMA I&T) with respect to efficacy and haematologic safety.
Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography (Ga-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed.
One hundred patients completed one cycle of Lu PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50-89), median number of prior therapies was three (1-6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months ( < 0.0001; 95% CI: 0.08-0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated.
Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.
转移性去势抵抗性前列腺癌（mCRPC）仍是全球癌症负担的重要因素。镥-177-前列腺特异性膜抗原放射性配体疗法（Lu-PSMA RLT）是一种有效的挽救性治疗方法。然而，研究强调血液学毒性是一个值得关注的不良事件。我们报告了我们单中心关于同情用药姑息性Lu-DOTAGA-(I-y)fk(Sub-KuE)（Lu-PSMA I&T）在疗效和血液学安全性方面的经验。
纳入mCRPC且骨髓/肝功能良好的患者。所有纳入患者均通过镓-68-PSMA-11正电子发射断层扫描/计算机断层扫描（Ga-PSMA-11 PET/CT）进行基线和反应评估。规定的治疗活度为每位患者每周期中位数6.24 GBq（IQR 1.29 GBq），每8周给药一次，最多四个周期。通过前列腺特异性抗原（PSA）和第12周的PET/CT评估反应。分析≥3级血液学毒性的发生率，包括与危险因素（年龄≥70岁、既往/同时进行的治疗、转移灶的存在以及完成的周期数）的关联。
100例患者完成了一个周期的Lu PSMA I&T治疗，并通过PSA和PET/CT进行了反应评估。2例患者第12周的PET/CT结果无法解读。中位年龄为70岁（50 - 89岁），既往治疗的中位次数为3次（1 - 6次），中位随访时间为12个月。54%的患者PSA有反应。PET/CT的疾病控制率（DCR）为64%（29%疾病稳定，34%部分缓解，1%完全缓解）。与无反应者相比，PET/CT的疾病控制与一年总生存期（OS）改善相关，中位OS未达到 vs 10个月（<0.0001；95%CI：0.08 - 0.44）。关于血液学毒性，11%的患者经历了≥3级血细胞减少（自限性）。未记录到骨髓发育异常/急性白血病（MDS/AL）病例。未显示与危险因素有关联。
Lu-PSMA I&T是一种安全有效的mCRPC姑息性门诊治疗方法。Ga-PSMA-11 PET/CT反应与一年OS改善相关，可用于调整治疗方案。
