Laboratory and clinical biomarkers proposed for therapeutic monitoring
| Therapeutic monitoring biomarker . | SCT or GT/E . | Direct or surrogate biomarker . | Biomarker value validation . |
|---|---|---|---|
| Laboratory biomarkers | |||
| Donor chimerism (%) | SCT/GT/E | Surrogate | Strong |
| Hb; reticulocyte (target; time to target) | SCT/GT/E | Surrogate | Strong |
| Increase in HbF (α2γ2) | GT/E | Surrogate | Strong |
| Increase in or HbA (α2β2) | SCT/GT/E | Surrogate | Strong |
| Clinical biomarkers | |||
| Change in TF requirements | SCT/GT/E | Direct | Intermediate* |
| Change in VOC | SCT/GT/E | Direct | Intermediate* |
| Change in all pain levels | SCT/GT/E | Direct | Intermediate* |
| Change in HRQoL | SCT/GT/E | Direct | Intermediate* |
| Change in organ-specific function | SCT/GT/E | Direct | Intermediate* |
| Therapeutic monitoring biomarker . | SCT or GT/E . | Direct or surrogate biomarker . | Biomarker value validation . |
|---|---|---|---|
| Laboratory biomarkers | |||
| Donor chimerism (%) | SCT/GT/E | Surrogate | Strong |
| Hb; reticulocyte (target; time to target) | SCT/GT/E | Surrogate | Strong |
| Increase in HbF (α2γ2) | GT/E | Surrogate | Strong |
| Increase in or HbA (α2β2) | SCT/GT/E | Surrogate | Strong |
| Clinical biomarkers | |||
| Change in TF requirements | SCT/GT/E | Direct | Intermediate* |
| Change in VOC | SCT/GT/E | Direct | Intermediate* |
| Change in all pain levels | SCT/GT/E | Direct | Intermediate* |
| Change in HRQoL | SCT/GT/E | Direct | Intermediate* |
| Change in organ-specific function | SCT/GT/E | Direct | Intermediate* |
GT/E, gene therapy/editing; SCT, stem cell therapy.
Could be strengthened by choosing targets that meet the FDA guidance for rare disease trial end points (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm613026.html).