Myelosuppression after radioligand therapy

Because radioligand therapies circulate systemically before binding their target, bone marrow receives incidental irradiation and can develop dose-related cytopenias. In the VISION trial of lutetium-177 vipivotide tetraxetan (Pluvicto) for metastatic castration-resistant prostate cancer, grade 3-4 laboratory abnormalities occurred in 15% of patients for decreased haemoglobin, 9% for decreased platelets, 7% for decreased leukocytes and 4.5% for decreased neutrophils; grade 3-4 pancytopenia occurred in 1.1% including two fatal events, and four myelosuppression-related deaths were reported in total (from intracranial or subdural haemorrhage associated with thrombocytopenia, sepsis with neutropenia, and bone marrow failure). In the earlier-line PSMAfore and PSMAddition trials, grade 3-4 rates were generally lower (for example, grade 3-4 decreased haemoglobin 7% and 4.3% respectively), consistent with less marrow reserve in more heavily pretreated VISION-era patients.

The Pluvicto label requires complete blood counts before and during treatment and specifies dose modifications for myelosuppression: withhold for grade 2, and withhold plus reduce the dose by 20% (to 5.9 GBq/160 mCi) for grade 3 or higher, with permanent discontinuation for recurrent grade 3 or higher myelosuppression after one dose reduction. Lymphopenia is the most frequent laboratory abnormality overall, reported in over 80-90% of patients at any grade in pooled analyses, reflecting the radiosensitivity of lymphocytes.

For peptide receptor radionuclide therapy with lutetium-177 dotatate, grade 3-4 haematological toxicity is less frequent, reported around 9-13% in cohort series, generally reversible, and less common than with the historical 90Y-labelled somatostatin analogues. Risk factors for more severe myelosuppression across radioligand therapies include extensive bone marrow involvement by tumour, prior chemotherapy or external beam radiotherapy, and impaired baseline renal function, since slower renal clearance prolongs the radiopharmaceutical's circulation time and marrow exposure.