How to handle side effects of CAR-T cell therapy

Immune-cell based therapies opening a new frontier for cancer treatment carry unique, potentially lethal side effects that provide a new challenge for oncologists, one addressed by a team led by clinicians at The University of Texas MD Anderson Cancer Center with proposed guidelines for systematically dealing with the toxicities of these drugs.

Their work, published recently in Nature Reviews Clinical Oncology, confronts the two main side effects of chimeric antigen receptor T cells, known as CAR T cells, white blood cells genetically engineered to strike cells with a specific target on their surface.

“CAR T cells provide an entirely new level of improved disease response among patients with certain blood cancers and hold promise for more wide-ranging use,” said Elizabeth Shpall, M.D., deputy chair and professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson.

“The algorithms that we published are conservative, detailed, and will help us save lives as we move forward with these exciting but also more toxic therapies,” Shpall said.

The review covers wide-ranging research on CAR-T therapies by many institutions and includes insights based on more than 100 patients treated at MD Anderson, Moffitt Cancer Center in Tampa, Sylvester Cancer Center at the University of Miami, and Mayo Clinic Cancer Center in Rochester, Minn.

Patients were treated by the co-authors with CAR T cells under development at four different companies for leukemias and lymphomas that attack white blood cells called B cells.  They target CD19, a protein found on the surface of both malignant and normal B cells.

Cytokine storms, brain stressors and safety

Two side effects have emerged during clinical trials that were previously uncommon to cancer treatments:

• Cytokine release syndrome (CRS), also known as cytokine storm, an escalated immune response that causes flu-like symptoms and can be fatal.
• Neurological toxicity that the researchers have named CAR-T-cell-related encephalopathy syndrome (CRES), which can sometimes lead to lethal swelling in the brain.

Both CRS and CRES are treatable, with early identification important to swift improvement. The review provides specific recommendations for pre-treatment preparation, monitoring of patients during and after CAR T infusion, identifying and staging emerging CRS and CRES, and tailored treatment of those side effects depending upon their severity.

Read more about the study in the MD Anderson Newsroom.