Predicting and Treating Dangerous Side Effects in CAR T-Cell Therapy

This patent describes methods to identify patients at high risk for severe side effects, like cytokine release syndrome or neurotoxicity, during CAR T-cell cancer therapy and how to treat them proactively.

What it covers

This patent outlines a method to reduce severe side effects, specifically severe cytokine release syndrome (CRS) or severe neurotoxicity, in patients receiving CAR T-cell therapy. The method involves administering a specific dose of CAR-expressing T cells, between 1.0x10^7 and 1x10^8 total cells. After the cells are given, the patient's blood is checked. If the CAR T-cells show a rapid expansion within about seven days (Claim 1), or if the level of interleukin-15 (IL-15) is high (at or above 30 pg/mL) within five days (Claim 2), or if specific CAR T-cell counts are met at certain days (e.g., at least 15 cells per microliter by day seven, Claim 16), the patient is identified as being at risk. Once identified, the patient is treated with an agent like a steroid (such as dexamethasone, Claim 9) or an IL-6 or IL-6 receptor inhibitor (like tocilizumab, Claim 10) to prevent or manage these severe toxicities.

What it doesn't cover

• —Does not cover CAR T-cell doses outside the specified range of 1.0x10^7 to 1x10^8 total cells.
• —Does not cover treating toxicities other than severe cytokine release syndrome or severe neurotoxicity.
• —Does not cover methods of toxicity management that do not involve administering a steroid or an IL-6 or IL-6 receptor inhibitor.
• —Does not cover risk assessment methods that do not rely on CAR T-cell expansion timing, specific cell counts at defined days, or IL-15 levels.
• —Does not cover CAR T-cell therapies where the CAR targets antigens unrelated to B cell malignancies, unless they are specifically listed antigens like CD19 or CD20.

The clever bit

The novelty lies in defining specific, measurable biological indicators and precise timing thresholds (like rapid T-cell expansion within seven days or specific IL-15 levels) that reliably predict severe toxicity *before* it becomes life-threatening, allowing for timely and targeted intervention.

Why it matters

CAR T-cell therapy is a powerful and life-saving treatment for certain blood cancers, but it carries significant risks, particularly severe cytokine release syndrome and neurotoxicity. This patent provides a structured, data-driven approach to identify patients at high risk for these dangerous side effects early. By enabling proactive intervention with specific medications, it helps make CAR T-cell therapies safer and more manageable, which is critical for their broader adoption and success in treating diseases like leukemia and lymphoma.

Real-world examples

• 1.Kymriah (tisagenlecleucel) for ALL and DLBCL
• 2.Yescarta (axicabtagene ciloleucel) for DLBCL and follicular lymphoma
• 3.Tecartus (brexucabtagene autoleucel) for mantle cell lymphoma and ALL
• 4.Most modern CAR T-cell therapy treatment protocols