Pluvicto Adverse Reactions

Summary of safety profile: Unless otherwise stated, the frequency of listed adverse reactions is based on data from the VISION study in which 529 patients received at least one dose of 7400 MBq (median number of doses was five).
The most common adverse reactions include: fatigue (43.1%), dry mouth (39.3%), nausea (35.3%), anaemia (31.8%), decreased appetite (21.2%) and constipation (20.2%). The most common grade 3 to 4 adverse reactions include: anaemia (12.9%), thrombocytopenia (7.9%), lymphopenia (7.8%) and fatigue (5.9%).
Tabulated list of adverse reactions: Adverse reactions (Table 4) are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. In addition, the corresponding frequency category for each adverse reaction is based on the following convention (CIOMS III): very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); very rare (<1/10000). (See Table 4.)

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Description of selected adverse reactions: Myelosuppression: In the VISION study, myelosuppression occurred more frequently in patients who received Pluvicto plus BSoC compared to patients who received BSoC alone (all grades/grade ≥3): anaemia (31.8%/12.9%) versus (13.2%/4.9%); thrombocytopenia (17.2%/7.9%) versus (4.4%/1.0%); leukopenia (12.5%/2.5%) versus (2.0%/0.5%); lymphopenia (14.2%/7.8%) versus (3.9%/0.5%); neutropenia (8.5%/3.4%) versus (1.5%/0.5%); pancytopenia (1.5%/1.1%) versus (0%/0%) including two fatal events of pancytopenia in patients who received Pluvicto plus BSoC; and bicytopenia (0.2%/0.2%) versus (0%/0%).
Myelosuppression adverse reactions that led to permanent discontinuation in ≥0.5% of patients who received Pluvicto plus BSoC included: anaemia (2.8%), thrombocytopenia (2.8%), leukopenia (1.3%), neutropenia (0.8%) and pancytopenia (0.6%). Myelosuppression adverse reactions that led to dose interruptions/dose reductions in ≥0.5% of patients who received Pluvicto plus BSoC included: anaemia (5.1%/1.3%), thrombocytopenia (3.6%/1.9%), leukopenia (1.5%/0.6%) and neutropenia (0.8%/0.6%).
Renal toxicity: In the VISION study, renal toxicity occurred more frequently in patients who received Pluvicto plus BSoC compared to patients who received BSoC alone (all grades/grades 3 to 4): blood creatinine increased (5.3%/0.2%) versus (2.4%/0.5%); acute kidney injury (3.6%/3.0%) versus (3.9%/2.4%); renal failure (0.2%/0%) versus (0%/0%); and blood urea increased (0.2%/0%) versus (0%/0%).
Renal adverse reactions that led to permanent discontinuation in ≥0.2% of patients who received Pluvicto plus BSoC included: blood creatinine increased (0.2%). Renal adverse reactions that led to dose interruptions/dose reductions in ≥0.2% of patients who received Pluvicto plus BSoC included: blood creatinine increased (0.2%/0.4%) and acute kidney injury (0.2%/0%).
Second primary malignancies: Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer and mutations. In all cases, it is necessary to ensure that the risks of the radiation are less than from the disease itself. As Pluvicto contributes to a patient's overall long-term radiation exposure, which is associated with an increased risk for cancer (see Precautions), a potential risk of second primary malignancies cannot be ruled out for radiopharmaceuticals such as Pluvicto. At the time of the VISION primary analysis (cut-off date 27-Jan-2021), cases of squamous cell carcinoma (4 patients; 0.8%) and basal cell carcinoma, malignant melanoma and squamous cell carcinoma of the skin (1 patient each; 0.2% each) were reported in patients who received Pluvicto plus BSoC.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.