用 psma-177lu 治疗难治性多发性骨髓瘤:病例报告

Kaique M. Amaral, Felipe P.G. Ribeiro, Fernando V.P. Souza, Allan O. Santos, Sergio Q. Brunetto, Maria Emilia S. Takahashi, Vania P. Castro, Carmem S.P. Lima, Barbara J. Amorim, Carmino A. Souza, Celso D. Ramos
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引用次数: 0

摘要

导言/理由三重难治性多发性骨髓瘤(MM)预后不良。它是一种具有明显基因组异质性的肿瘤,最近,我们的研究小组在一些患者中证实了68Ga-PSMA-11的明显摄取,这表明PSMA在选定病例中具有潜在的治疗作用(1)。报告一名 76 岁的 IgA/Kappa MM 男性患者,对达拉单抗、来那度胺和硼替佐米等 6 种疗法均难治,接受了 18F-PSMA-1007 的 PET/CT 检查,结果显示多处溶骨性病变有明显的示踪剂摄取,其中几处还伴有广泛的软组织成分。此外,还进行了 18F-FDG PET/CT,也发现了类似的结果。第一剂量为 7,400 MBq(200 mCi)的 177Lu-PSMA-I&T。手术耐受性良好,输注后一周内临床症状略有改善。对 21 小时、30 小时和 7 天后进行的全身扫描的目视分析表明,示踪剂摄取量适中,低于 18F-PSMA-1007 观察到的摄取量。21 小时和 30 小时的图像之间有轻微的洗脱,7 天后有中度/明显的洗脱。4 周后,再次使用 18F-PSMA 和 18F-FDG 进行 PET/CT 扫描,结果与最初的扫描结果相似,某些病灶的示踪剂摄取量略有减少。一些软组织病变的体积也有所增加,这归因于治疗后的炎症。6 周后,患者接受了第二次剂量为 7,400 MBq(200 mCi)的 177Lu-PSMA-I&T 治疗,并在 2h 和 24h 时进行了全身扫描,结果显示摄取量明显低于 18F-PSMA-1007。结论这份初步报告表明,用 177Lu-PSMA 治疗 MM 是可行的,而且在首次用药 2 次后耐受性良好。从视觉上看,177Lu-PSMA-I&T 的摄取量低于 18F-PSMA-1007,这似乎并不完全是由于不同示踪剂和设备获得的图像分辨率不同造成的。在总共 6 次计划用药中,第一次用药后出现了轻微的临床和成像反应。由于骨折并发症和病例的严重性,第二次用药后无法进行成像评估,也无法继续治疗。PSMA-177Lu治疗MM似乎是安全的,尽管反应轻微,但初期反应良好。要评估该疗法的有效性,还需要对临床症状较轻的患者进行完整治疗(6 个周期)的研究。
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TREATMENT OF REFRACTORY MULTIPLE MYELOMA WITH PSMA-177LU: A CASE REPORT

Introduction/Justification

Triple-refractory multiple myeloma (MM) has a poor prognosis. It is a neoplasm with marked genomic heterogeneity, and recently, our group demonstrated marked uptake of 68Ga-PSMA-11 in some patients, suggesting the potential theranostic use of PSMA in selected cases (1). Herein, we report the initial treatment with 177Lu-PSMA in a patient with refractory MM.

Report

A 76-year-old male patient with IgA/Kappa MM refractory to 6 therapeutic lines, including daratumumab, lenalidomide, and bortezomib, underwent PET/CT with 18F-PSMA-1007, showing marked tracer uptake in multiple osteolytic lesions, several with extensive soft tissue components. A PET/CT with 18F-FDG was also performed, revealing similar findings. A first dose of 7,400 MBq (200 mCi) of 177Lu-PSMA-I&T was administered. The procedure was well tolerated, with slight clinical improvement observed in the week following the infusion. Visual analysis of whole-body scans performed at 21h, 30h, and 7 days demonstrated moderate tracer uptake, lower than that observed with 18F-PSMA-1007. There was slight washout between images at 21h and 30h and moderate/significant washout after 7 days. After 4 weeks, PET/CTs with 18F-PSMA and 18F-FDG were repeated, showing similar findings to the initial scans, with a slight reduction in tracer uptake in some lesions. There was also an increase in the volume of some soft tissue lesions, attributed to post-treatment inflammation. The patient received a second dose of 7,400 MBq (200 mCi) of 177Lu-PSMA-I&T after 6 weeks, and whole-body scans were performed at 2h and 24h, also showing visually lower uptake compared to 18F-PSMA-1007. The patient experienced an intercurrent femoral fracture, limiting mobility for clinical evaluation and subsequent procedures, ultimately leading to their passing after a few days.

Conclusion

This preliminary report suggests that treatment of MM with 177Lu-PSMA is feasible and well tolerated after 2 initial doses. The uptake of 177Lu-PSMA-I&T was visually lower than that of 18F-PSMA-1007, which does not seem to be solely explained by the different resolution of images obtained from different tracers and equipment. There was a slight clinical and imaging response after the first dose, out of a total of 6 planned. A fracture complication and the severity of the case prevented imaging evaluation after the 2nd dose and further treatment continuation. PSMA-177Lu therapy in MM treatment appears to be safe with an initial favorable response, albeit slight. Studies with complete treatments (6 cycles) and in clinically less severe patients are needed to assess the effectiveness of the procedure.

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