Tolerability of Lutetium-177-PSMA-617 in Patients With Prostate Cancer, Cytopenia

New research sheds light on the safety of lutetium-177 (¹⁷⁷Lu)–PSMA-617 for patients with metastatic castration-resistant prostate cancer (mCRPC) and poor bone marrow reserve.

Results of the VISION trial led to the US Food and Drug Administration’s approval of (¹⁷⁷Lu)–PSMA-617 for the treatment of mCRPC. However, the trial excluded patients with baseline cytopenias—a large proportion of this patient population.

Mohamed E. Ahmed, MD, and colleagues designed a retrospective analysis using real-world data to better understand the tolerability of radioligand therapy in patients with cytopenias. They reviewed the records of all patients who received a first dose of (¹⁷⁷Lu)–PSMA-617 at the Mayo Clinic from April to December 2022. As per the parameters of the VISION trial, patients were categorized as having poor marrow reserve based on pre-treatment hematologic parameters, including an anemia cohort with hemoglobin less than 9 g/dL, a thrombocytopenia cohort with platelets less than 100 x 109/L, a leukopenia cohort with white blood cell count less than 2.5 x 109/L, and a multiple cytopenia cohort.

Researchers collected and analyzed longitudinal laboratory data and clinical outcomes using descriptive statistics. The results of the analysis were presented at the 24^th Annual Meeting of the Society of Urologic Oncology .

A total of 273 patients who received at least 1 dose of (¹⁷⁷Lu)–PSMA-617 were identified, including 33 patients with at least 1 baseline cytopenia before their first cycle of treatment. Among this group, 25 had anemia, 4 had thrombocytopenia, 2 had leukopenia, and 2 had multiple cytopenias.

Researchers noted a median of 4 (¹⁷⁷Lu)–PSMA-617 cycles received, including 21 patients who are still receiving therapy and 12 patients who have permanently discontinued treatment. Reasons for treatment discontinuation included toxicity (n=5), disease progression (n=4), and death (n=8). Among the patients who stopped therapy due to toxicity or disease progression, 5 have died.

In addition, the researchers reported that dose reductions (n=8) or treatment delays (n=8) for worsening myelosuppression occurred, and transfusions of packed red blood cells or platelets were required for 26 patients. Sixteen patients received care in the emergency department or were hospitalized.

“Treatment discontinuation for toxicity was rare among men with mCRPC and baseline cytopenias while receiving (¹⁷⁷Lu)–PSMA-617,” Dr. Ahmed and colleagues concluded, acknowledging that these patients have an overall poor prognosis.