Treatment with ¹⁷⁷Lu-PSMA-617 (lutetium Lu 177 vipivotide tetraxetan; Pluvicto) is tolerable in patients with metastatic castration-resistant prostate cancer (mCRPC) and baseline cytopenias, according to a retrospective study presented at the 2023 Society of Urologic Oncology (SUO) Annual Meeting.1

“The majority of patients were able to complete the treatment, receiving a median of 4 treatment cycles,” said presenting author Mohamed E. Ahmed, MD, department of Urology, Mayo Clinic. “Treatment discontinuation for toxicity was rare among men with mCRPC and baseline cytopenias receiving ¹⁷⁷Lu-PSMA-617; however, these patients have an overall poor prognosis,” added Ahmed.

Ahmed et al explained that the pivotal VISION trial (NCT03511664) that supported the FDA approval of ¹⁷⁷Lu-PSMA-617 for the treatment of patients with mCRPC did not enroll patients with baseline cytopenias. Accordingly, the investigators sought to examine the tolerability of ¹⁷⁷Lu-PSMA-617 in patients with “poorer bone marrow reserve.”1

Ahmed and colleagues at the Mayo Clinic conducted a retrospective review of the medical records of patients treated with a first dose of ¹⁷⁷Lu-PSMA-617 at the institution between April 26 and December 1, 2022. Pre-treatment hematologic parameters were used to identify patients with poor marrow reserve. According to the researchers’ SUO poster, some of these parameters included:

• Anemia with hemoglobin less than 9 g/dL
  

• Thrombocytopenia cohort with platelets less than 100 x 109/L
  

• Leukopenia cohort with white blood cell (WBC) count less than 2.5 x 109/L
  

• Multiple cytopenia cohort

The review found that 185 patients had been treated with at least 1 dose of ¹⁷⁷Lu-PSMA-617. Of these patients, 26 (14%) had ≥1 baseline cytopenia prior to receiving their first treatment cycle. Across the 26 patients, 19 had anemia, 3 had thrombocytopenia, 2 had leukopenia, and 2 had multiple cytopenias at baseline.

The median age at diagnosis of the 26 patients was 62.5 years (interquartile range [IQR], 57.5-67.3). Initial Gleason Scores were as follows: 6 (n = 2), 7 (n = 5), 8 (n = 4), 9 (n = 6), 10 (n = 2), and not available (n = 7). ECOG performance status included 0 (n = 9), 1 (n = 12), and 2 (n = 5).

At the administration of their first ¹⁷⁷Lu-PSMA-617 cycle, patients had a median age of 70 years (IQR, 65.75-77.5) and a median PSA level of 94 ng/ml (IQR, 6-334.3). At a median follow-up time of 12.3 months (IQR, 7.2-18.5), patients had received a median of 4 ¹⁷⁷Lu-PSMA-617 cycles (IQR, 3-5).

Of the 26 patients, 12 patients had to discontinue treatment. Only 2 of these patients discontinued due to toxicity. The other reasons for discontinuation included disease progression (n = 5), death (n = 4), other (n = 1).

Worsening myelosuppression led to dose reductions in 3 patients and treatment delays in 5 patients. Sixteen patients needed transfusions of packed red blood cells or platelets. There were 6 patients who either had go to the emergency room or required hospitalization.

The researchers also examined median longitudinal changes in blood counts. Ahmed noted that this analysis did show areas to monitor in which the counts decreased. For example, the platelet count dropped in the anemia (159 to 75) and multiple cytopenias (93 to 60) cohorts from cycle 1 to cycle 5. Similarly, in the thrombocytopenia cohort, the platelet count dropped from 92 in cycle 1 to 75 in cycle 4.

Ahmed said that these drops were “very well managed,” and that they were able to give transfusions when necessary.

¹⁷⁷Lu-PSMA-617 is approved by the FDA for the treatment of adult patients with PSMA-positive mCRPC who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy.2

References

1. Ahmed ME, Mahmoud AM, Abdelrazek AS, et al. Tolerability of lutetium-177–PSMA-617 in men with prostate cancer and baseline cytopenia. Presented at: 2023 Society of Urologic Oncology Annual Meeting. November 28 – December 1, 2023; Washington, DC. Abstract 28.

2. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. Published online March 23, 2022. Accessed November 29, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer