Mechanisms of kinase inhibitor resistance in subtypes of cutaneous T-cell lymphomas
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By
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Julia A. Yescas
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Christopher G. Bunick
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Ayman Grada
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Joan Guitart
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Carlos A. Torres-Cabala
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I. Caroline Le Poole
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Xiaolong A. Zhou
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May 13, 2026
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Clinical Scorecard: Resistance Mechanisms to Kinase Inhibitors in Various Subtypes of Cutaneous T-Cell Lymphomas
At a Glance
| Category | Detail |
|---|
| Condition | Cutaneous T-cell lymphomas (CTCLs) |
| Key Mechanisms | Alterations in tyrosine kinase signaling pathways, including JAK/STAT and FGFR pathways. |
| Target Population | Patients with primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma (PCAETL) and primary cutaneous gamma/delta T-cell lymphoma (PCGDTL). |
| Care Setting | Oncology and dermatology clinics. |
Key Highlights
- PCAETL and PCGDTL exhibit recurrent kinase fusions and activating mutations.
- Tyrosine kinase inhibitors (TKIs) show potential but often lead to resistance.
- Acquired resistance mechanisms include secondary kinase domain mutations.
- Longitudinal genomic monitoring is essential for managing resistance.
- PCAETL and PCGDTL represent a model for precision oncology in dermatology.
Guideline-Based Recommendations
Diagnosis
- Utilize genomic studies to identify kinase fusions and mutations.
Management
- Consider targeted therapy with TKIs for patients with identified kinase alterations.
Monitoring & Follow-up
- Implement longitudinal genomic monitoring to detect resistance mutations.
Risks
- Monitor for adverse events that may necessitate dose reductions, leading to resistance.
Patient & Prescribing Data
Patients with aggressive subtypes of CTCL, particularly PCAETL and PCGDTL.
TKIs like ruxolitinib, cerdulatinib, and pemigatinib can provide meaningful responses but may be transient.
Clinical Best Practices
- Stratify patients based on molecular profiles for targeted therapies.
- Adopt combination strategies to overcome resistance mechanisms.
- Educate patients on the potential for adverse effects and resistance.
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