Can Pluvicto Cause LDH Elevation in Prostate Cancer Patients?
Yes, Pluvicto (lutetium Lu 177 vipivotide tetraxetan) infusions can be associated with elevated LDH levels, though this is not a direct drug toxicity but rather reflects tumor burden, disease progression, or tumor lysis during treatment. 1, 2
Understanding LDH (Lactate Dehydrogenase)
LDH is a non-specific enzyme released during cellular injury or lysis from virtually any tissue. 3
- LDH elevations occur with strenuous exercise, liver disease, myocardial infarction, kidney disease, hemolysis, pneumonia, and countless other conditions causing cellular damage 3
- In prostate cancer specifically, elevated LDH is a prognostic marker associated with worse outcomes, particularly in metastatic castration-resistant prostate cancer (mCRPC) 3
- LDH is not a tumor-specific marker but rather indicates high tumor burden, aggressive disease biology, or rapid cell turnover 3
LDH in the Context of Pluvicto Treatment
Baseline LDH as a Prognostic Factor
- In the VISION trial that led to Pluvicto's approval, baseline LDH was used as a stratification factor for randomization, recognizing its prognostic significance 1, 4
- Elevated baseline LDH predicts shorter progression-free survival and overall survival in patients receiving PSMA-targeted radioligand therapy 2
- Rising LDH during treatment is associated with worse treatment outcomes and shorter survival 2
Mechanisms of LDH Elevation During Pluvicto Treatment
LDH can rise during Pluvicto infusions through several mechanisms:
- Tumor lysis: As Pluvicto delivers targeted radiation to PSMA-expressing cancer cells, rapid tumor cell death releases intracellular LDH into the bloodstream 3, 1
- Disease progression: Rising LDH may indicate progressive disease rather than treatment effect 2
- Bone marrow toxicity: Pluvicto can cause hematologic toxicity (anemia in 15%, thrombocytopenia in 9%, neutropenia in 6%), and bone marrow cell damage releases LDH 4, 5
Clinical Context for Interpretation
When evaluating LDH elevations during Pluvicto therapy, consider the following algorithm:
- Timing of elevation: Early rises (within first 1-2 weeks) may represent tumor lysis, similar to patterns seen with chemotherapy 3
- Magnitude of change: Modest elevations (1.5-2x baseline) with clinical improvement suggest tumor lysis; progressive rises suggest disease progression 2
- Associated findings: Check for hemolysis markers (haptoglobin, indirect bilirubin), liver function tests, and renal function to exclude non-tumor causes 3, 1
- PSA correlation: If PSA is declining while LDH rises transiently, this favors tumor lysis; if both rise together, this suggests progression 2
Monitoring Recommendations
Patients receiving Pluvicto require regular laboratory monitoring:
- Complete blood counts should be checked before each dose (absolute neutrophil count ≥1.5 × 10⁹/L initially, ≥1 × 10⁹/L for subsequent doses; platelets ≥100 × 10⁹/L initially, ≥50 × 10⁹/L subsequently; hemoglobin ≥10 g/dL) 1, 5
- LDH should be monitored as part of disease assessment, though specific monitoring intervals are not mandated by the FDA label 1
- Patients with visceral metastases and elevated LDH at baseline represent a poor prognostic subgroup with shorter progression-free survival (1.7 months vs 7.5 months in those without these features) 3, 2
Clinical Implications
- LDH elevation alone should not prompt discontinuation of Pluvicto unless accompanied by clear evidence of disease progression or unacceptable toxicity 1, 5
- The most common laboratory abnormalities worsening from baseline in ≥30% of patients receiving Pluvicto are decreased lymphocytes, hemoglobin, leukocytes, platelets, calcium, and sodium—not elevated LDH 4
- Severe hematologic toxicity (grade 3-4) occurs in a minority: anemia 9%, thrombocytopenia 4%, neutropenia 6% 4