Dostarlimab and Cardiomyopathy Risk
Dostarlimab has not been associated with cardiomyopathy in clinical trials or post-marketing surveillance. While several cancer therapies are known to cause cardiotoxicity, current evidence does not indicate dostarlimab as a cause of cardiomyopathy.
Cancer Therapies Known to Cause Cardiomyopathy
Certain cancer therapies have well-documented cardiotoxic effects:
- Anthracyclines: High risk of cardiomyopathy with dose-dependent relationship (5% at 400 mg/m², 16% at 500 mg/m², 26% at 550 mg/m², and 48% at 700 mg/m²) 1
- Trastuzumab: 2-7% incidence of heart failure, increasing to 27% when used with anthracyclines 1
- Tyrosine kinase inhibitors: 3-15% cardiac dysfunction, 1-10% symptomatic heart failure 1
- Proteasome inhibitors: Bortezomib and carfilzomib target pathways common to cancer cells and vulnerable myocardium 2, 1
Evidence Regarding Dostarlimab
Dostarlimab is a humanized monoclonal antibody that binds to PD-1, inhibiting its interaction with PD-L1 and PD-L2 3, 4. The GARNET trial, which led to dostarlimab's approval for endometrial cancer, reported:
- Most common treatment-related adverse events were fatigue (17.6%), diarrhea (13.8%), and nausea (13.8%) 3
- Grade ≥3 treatment-related adverse events occurred in 16.6% of patients 3
- No cardiac-specific adverse events were highlighted as significant concerns 3
A specific cardiac safety study examining dostarlimab's effect on QT interval found:
- No clinically significant QTcF prolongation 5
- No reports of torsades de pointes, ventricular tachycardia, or ventricular fibrillation/flutter 5
- No mention of cardiomyopathy as an adverse event 5
Monitoring Recommendations
While dostarlimab has not been associated with cardiomyopathy, prudent monitoring is reasonable when using any cancer therapy:
- Baseline cardiac evaluation including LVEF assessment before starting treatment 2
- Consider cardiac biomarkers (troponin, BNP) for early detection of potential myocardial injury 1
- Regular follow-up for patients with pre-existing cardiovascular risk factors
Clinical Implications
When considering dostarlimab therapy:
- No specific cardiac monitoring is required based on current evidence
- Standard cancer therapy monitoring protocols are appropriate
- Unlike anthracyclines or trastuzumab, there is no need for routine cardiac function assessment during dostarlimab therapy
Pitfalls and Caveats
- Cancer therapies are constantly evolving, and rare adverse events may emerge with wider use
- Patients receiving multiple cancer therapies may have cumulative cardiotoxic risk
- Elderly patients or those with pre-existing cardiovascular disease may require closer monitoring regardless of the specific therapy used
In conclusion, current evidence does not support dostarlimab as a cause of cardiomyopathy, unlike several other established cancer therapies with known cardiotoxic effects.