Long-Term Nephrotoxicity of 177Lu-PSMA Radioligand Therapy

Lisa Steinhelfer; Lukas Lunger; Lisena Cala; Christian H. Pfob; Constantin Lapa; Philipp E. Hartrampf; Andreas K. Buck; Hannah Schäfer; Christoph Schmaderer; Robert Tauber; Julia Brosch-Lenz; Bernhard Haller; Valentin H. Meissner; Karina Knorr; Wolfgang A. Weber; Matthias Eiber

doi:10.2967/jnumed.123.265986

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FIGURE 1.
Box plots illustrating percentage eGFR decrease from baseline after initiation of ¹⁷⁷Lu-PSMA. × within box plots = mean.
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FIGURE 2.
Individual percentage changes in eGFR from baseline in 58 patients with ≥3% eGFR decline at 3 mo (left) and 48 patients with <3% or no eGFR decline at 3 mo (right) after ¹⁷⁷Lu-PSMA RLT. Dashed line indicates expected age-associated yearly eGFR decline of 1 mL/min for 70-y-old-man without comorbidities, assuming baseline GFR of 85 mL/min. Thus, after 3 y, eGFR would have declined by 3% from baseline in this healthy man.

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TABLE 1.

Patient Characteristics (n = 106)

Characteristic	Data
Mean age (y)	73 (SD, 7)
Mean baseline eGFR (mL/min)	84 (SD, 27)
Prior treatment lines
Abiraterone	87 patients (82%)
Enzalutamide	67 patients (63%)
Docetaxel	60 patients (57%)
Cabazitaxel	16 patients (15%)
²²³Ra-dichloride	8 patients (8%)
Platinum-based chemotherapy	3 patients (3%)
¹⁷⁷Lu-PSMA cycles
Median	6 cycles (IQR, 5–8)
<6 cycles	33 patients (31%)
≥6 cycles	73 patients (69%)
Risk factors before ¹⁷⁷Lu-PSMA treatment^*
0	6 patients (6%)
1	18 patients (16%)
2	43 patients (41%)
3	34 patients (32%)
4	5 patients (5%)

↵* Arterial hypertension, diabetes mellitus, age ≥ 65 y, prior platinum-based chemotherapy.

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TABLE 2.
Proportion of Patients with eGFR Decreases by ≥15% 1 Year After Initiation of ¹⁷⁷Lu-PSMA
eGFR decrease/y Patients (n)
Total ≥ 15% 48 (45%)
≥15%–<30% 23 (48%)
≥30%–<40% 12 (25%)
≥40% 13 (27%)
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TABLE 3.
Distribution of Renal Failure Stages at Baseline and 1 Year After Initiation of ¹⁷⁷Lu-PSMA (n = 106)
Chronic kidney disease stage Baseline (n) 12 mo (n)
1 (>90 mL/min) 43 (40%) 22 (21%)
2 (60–89 mL/min) 42 (40%) 43 (41%)
3 (30–59 mL/min) 21 (20%) 40 (37%)
4 (15–29 mL/min) 0 1 (1%)

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TABLE 4.

Multivariable Linear Regression Model for Association of Risk Factors, Pretreatment Lines, and ¹⁷⁷Lu-PSMA Cycles Received by 12 Months with Percentage Decrease in eGFR 12 Months from Initiation of ¹⁷⁷Lu-PSMA

Variable (n)	B	95% CI	β	t	p
Risk factors at baseline	−4.51	−8.52 to −0.50	−0.24	−2.23	0.03
Treatment lines before ¹⁷⁷Lu-PSMA	2.53	−0.68 to 5.74	0.15	1.56	0.12
Cycles of ¹⁷⁷Lu-PSMA	−1.30	−3.71 to 1.12	−0.11	−1.06	0.29

R² adjusted = 0.057 (n = 106). P = 0.029. B = estimated coefficient for predictor variable; β = standardized coefficient (β weight); t = t-statistical for testing significance of coefficient; p = p-value.