Background: Despite the therapeutic advances made in castration-sensitive prostate cancer, progression to castration-resistant disease is inevitable. Lutetium-177 vipivotide tetraxetan (177Lu-PSMA-617) is a novel radioligand approved for use in metastatic castration-resistant prostate cancer (mCRPC). With promising efficacy, it is not without numerous potential side effects, namely cytopenias, which are often a reason for early discontinuation of 177Lu-PSMA-617. We sought to describe the incidence of cytopenias associated with permanent discontinuation of 177Lu-PSMA-617 at our institution. Methods: We conducted a retrospective review of patients who received 177Lu-PSMA-617at the University of Virginia Comprehensive Cancer Center from 2018 to 2025. From this we assessed for the incidence of toxicities resulting in permanent discontinuation of 177Lu-PSMA-617, which we refer to as dose-limiting toxicities. Descriptive statistics were used to summarize characteristics of the study population. Median overall survival from time of initiation of 177Lu-PSMA-617 was estimated using a Kaplan–Meier curve. Results: Of the patients who received 177Lu-PSMA-617 (n = 64), grade 3 or greater anemia occurred in 36% (n = 23), thrombocytopenia in 3% (n = 2), leukopenia in 3% (n = 2), neutropenia in 0% (n = 0), and lymphopenia in 33% (n = 21). In our cohort, 10.9% (n = 7) developed toxicities necessitating permanent discontinuation. Of these, 9.3% (n = 6) were attributable to cytopenias. Those cytopenias consisted of anemias in 100% (n = 6) of cases, leukopenia in 83% (n = 5), thrombocytopenia in 67% (n = 4), lymphopenia in 100% (n = 6), and neutropenia in 33% (n = 2). Aside from cytopenias, the remaining 1.6% (n = 1) of dose-limiting toxicities were attributable to renal injury. In the VISION trial, the 177Lu-PSMA-617 treatment arm reported dose-limiting toxicities necessitating permanent discontinuation in 11.9% of participants, but did not report if these were attributable to cytopenia or other toxicities. Notably, 2 patients developed grade 5 pancytopenia and 1 patient developed grade 5 bone marrow failure in the VISION 177Lu-PSMA-617 treatment arm. Compared to the VISION 177Lu-PSMA-617 treatment arm, our cohort differed in the distribution of organ metastases, younger median age of patients, and a higher portion of those with ECOG 2 functional status. From the time of 177Lu-PSMA-617 initiation, median overall survival was estimated to be 18.5 months, compared to 15.3 months in the VISION 177Lu-PSMA-617 treatment arm. Conclusions: In our real-world analysis, 85% of dose-limiting toxicities necessitating 177Lu-PSMA-617 discontinuation were attributed to cytopenias. Though a direct comparison cannot be made with the VISION 177Lu-PSMA-617 treatment arm in terms of dose-limiting toxicity attributable specifically to cytopenias, they reported total dose-limiting toxicity to a similar degree, and cytopenias were the most common causes of grade 3 or greater toxicities. Therefore, it is important to recognize the ubiquity of these adverse events as well as the role that they play in therapy-limiting toxicity.
Adler et al. (Fri,) studied this question.