Department of Nuclear Medicine, Medical University of Innsbruck, Anichstraße 35, Innsbruck, 6020, Austria.
Department of Experimental and Clinical Medicine, "Magna Graecia" University of Catanzaro, Catanzaro, Italy.
Eur J Nucl Med Mol Imaging. 2024 Dec;52(1):354-365. doi: 10.1007/s00259-024-06905-5. Epub 2024 Sep 3.
The purpose of this study was to evaluate the safety and outcome of rechallenge [Lu]Lu-PSMA-I&T in newly progressed mCRPC patients after response to initial [Lu]Lu-PSMA radioligand therapy (PRLT).
We retrospectively included 18 patients who underwent rechallenge with [Lu]Lu-PSMA-I&T. All patients presented with (i) newly progressed disease after response to initial PRLT; (ii) a [Ga]Ga-PSMA-11 PET/CT confirming the presence of PSMA-positive metastases; iii) ECOG performance status 0-1. Adverse events were graded according to CTCAE v5.0. Response was assessed by PSA and classified according to PCWG3 recommendations. For patients who underwent restaging with [Ga]Ga-PSMA-11 PET/CT, imaging response was categorised according to adapted PERCIST v1.0. In patients with discordant [Ga]Ga-PSMA-11 PET/CT and PSA, other available imaging modalities were evaluated to confirm disease status. Overall survival (OS) was calculated from the first cycle of initial PRLT and rechallenge PRLT, respectively, until last patient contact or death.
Patients were initially treated with a median of 5 cycles (range 4-7) and were rechallenged after a median of 9 months (range 3-13). Each patient received a median of 4 (range 2-7) rechallenge cycles (median cumulative activity 26.1 GBq). None of the patients experienced life-threatening G4 adverse events during either treatment period. Grade 3 adverse events included one case of anaemia, one case of thrombocytopenia, and one case of renal failure. In 8/18 patients long-term toxicities were evaluated. Serious toxicities (≥ Grade 3) occurred in 3/8 patients (n = 1 G4 thrombocytopenia, n = 1 G4 renal failure and n = 1 pancytopenia and G4 renal failure). Best PSA50%-response was observed in 44% of patients and PSA-disease control was confirmed in 56% of patients at the last cycle. Of the 12/18 patients restaged by imaging, 6/12 (50%) patients had disease control (partial response/stable disease), 1/12 had a mixed response, and 5/12 had progression. After a median follow-up time of 25 months (range 14-44), 10 patients had died, 7 were still alive, and one patient was lost at follow-up. The median OS was 29 months (95%CI, 14.3-43.7 months) for the initial treatment and 11 months (95%CI, 8.1-13.8 months) for the first rechallenge course.
More than half of patients benefit from rechallenge PRLT. Our analysis suggests that rechallenge may prolong survival in selected patients, with an acceptable safety profile.
本研究旨在评估在初始 LuPSMA 放射性配体治疗 (PRLT) 后对新进展的 mCRPC 患者进行 LuLu-PSMA-I&T 再挑战的安全性和结局。
我们回顾性纳入了 18 例接受 LuLu-PSMA-I&T 再挑战的患者。所有患者均表现为：(i)初始 PRLT 后疾病进展；(ii) GaPSMA-11 PET/CT 证实存在 PSMA 阳性转移灶；(iii) ECOG 体能状态 0-1。不良事件按 CTCAE v5.0 分级。根据 PCWG3 建议评估反应。对于接受 GaPSMA-11 PET/CT 再分期的患者，根据改编的 PERCIST v1.0 对影像学反应进行分类。对于 GaPSMA-11 PET/CT 和 PSA 结果不一致的患者，评估其他可用的影像学方法以确认疾病状态。分别从初始 PRLT 和再挑战 PRLT 的第一周期开始计算总生存期 (OS)，直至最后一次患者随访或死亡。
患者最初接受了中位数为 5 个周期 (范围 4-7) 的治疗，在中位数为 9 个月 (范围 3-13) 后再次接受了治疗。每位患者接受了中位数为 4 个 (范围 2-7) 的再挑战周期 (中位数累积活度 26.1GBq)。在这两个治疗期间，均无患者发生危及生命的 4 级不良事件。3 级不良事件包括 1 例贫血、1 例血小板减少症和 1 例肾功能衰竭。在 18 例患者中的 8 例中评估了长期毒性。3/8 例患者发生严重毒性 (≥3 级) (n=1 例 4 级血小板减少症，n=1 例 4 级肾功能衰竭和 n=1 例全血细胞减少症和 4 级肾功能衰竭)。在最后一个周期，44%的患者观察到最佳 PSA50%反应，56%的患者 PSA 疾病得到控制。在接受影像学检查的 12 例患者中有 6/12 (50%)患者疾病得到控制 (部分缓解/稳定疾病)，1/12 例患者混合反应，5/12 例患者进展。在中位随访时间为 25 个月 (范围 14-44)后，10 例患者死亡，7 例仍存活，1 例患者失访。初始治疗的中位 OS 为 29 个月 (95%CI，14.3-43.7 个月)，首次再挑战疗程的中位 OS 为 11 个月 (95%CI，8.1-13.8 个月)。
超过一半的患者从再挑战 PRLT 中获益。我们的分析表明，再挑战可能会延长选定患者的生存时间，且具有可接受的安全性。
