CAR T-Cell Therapy: What to Expect

TON - July 2017, Vol 10, No 4 - Conference Correspondent
Alice Goodman

Denver, CO—Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of some hematologic malignancies. This treatment is still investigational, and none of the CAR T-cell products being studied have received FDA approval yet, but approval is expected soon. Clinical trials involving CAR T-cell have shown dramatic results in patients who are terminally ill with hematologic malignancies and have no other treatment options, with a substantial portion of patients having long-lasting responses and remissions.

CAR T-cell is a “designer therapy” built from each patient’s T-cells, which are removed from the patient’s body via apheresis and genetically engineered ex vivo to express a receptor that recognizes an antigen on the patient’s tumor cells. The activated T-cells are reinfused into the patient where they expand and attack the cancer. CD19 CAR T-cell therapies have been studied most extensively.

CAR T-cell is not a benign therapy; it unleashes the patient’s immune system, and, in addition to attacking the cancer, can cause serious immune-related adverse events. At the 42nd annual meeting of the Oncology Nursing Society, Karen Anderson, MN, RN, AOCNS, BMTCN, CRNI, Immunotherapy Clinical Operations Manager, Seattle Cancer Care Alliance, WA, reviewed what is known about CAR T-cell therapy, and the nurse’s role in caring for patients treated with this novel approach.

“CAR-T therapy has opened up a whole new treatment paradigm for acute lymphocytic leukemia and other CD19-expressing cancers. CD19 CAR-T has achieved remissions in acute lymphocytic leukemia, non-Hodg­kin lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia,” Ms Anderson told attendees.

In studies thus far, CD19 CAR T-cell therapy has achieved a 93% complete remission rate in acute lymphocytic leukemia, a 72% objective response rate in non-Hodgkin lymphoma, a 47% complete remission rate in diffuse large B-cell lymphoma, and a 76% objective response rate in chronic lymphocytic leukemia.

“We know a lot about CD19 CAR T-cells, and other antigen targets are in current trials....CAR T-cells are living therapies that interact with cells, move into tissues, proliferate, and release cytokines. Along with this you see toxicity. The first several weeks are high-risk for toxicity, but toxicity can occur further down the line,” Ms Anderson continued.

Before CAR T-cell infusion, clinical trial eligibility is determined, patients undergo apheresis to collect T-cells, these T-cells are engineered ex vivo, and the disease is staged. During CAR T-cell infusion, patients receive lympho-depleting chemotherapy, and then T-cells are infused. Following CAR T-cell infusion, toxicity monitoring is initiated, the disease is restaged, and patients undergo long-term follow-up.

Toxicities

Data on toxicities come from clinical trials. Ms Anderson focused her remarks on the 2 adverse events of greatest concern—cytokine release syndrome (CRS) and neurotoxicity.

“Toxicities can be on-target and off-tumor. For every new antigen target, we will need to know where in the body that antigen is expressed. CD19-targeted CAR-T attack the B-cells, and that includes normal B-cells. The normal B-cells will not be able to secrete globulins, so patients given this therapy will need intravenous immunoglobulin to decrease the risk of infection,” Ms Anderson explained.

CRS is an inflammatory process characterized by elevated cytokines. Signs and symptoms can include high fever, tachycardia, capillary leak syndrome, hypoxia, hypotension, reduced liver or kidney function, and coagulopathies. Symptoms often begin with a flu-like syndrome that can rapidly progress to multiorgan dysfunction and death. CRS typically occurs within the first few weeks of CAR T-cell treatment.

Grade 1 CRS is non–life-threatening. Patients should be given supportive care and assessed and treated for infection. If significant fever is present, patients should be admitted to the hospital. Grade 2, 3, and 4 CRS require nursing care.

“Grade 2 CRS is a big bucket. It might emerge as mild then begin to progress,” Ms Anderson said.

Grade 2 CRS is treated with supportive care, and admission to the intensive care unit may be indicated. For high-risk patients, the administration of tocilizumab (an interleukin-6 inhibitor) and corticosteroids should be considered.

Grades 3 and 4 CRS require intensive care unit admission, supportive care, corticosteroids, and tocilizumab.

Neurotoxicity is another concern with CAR T-cell therapy. According to Ms Anderson, speech that is a “word salad” is a tip-off for neurotoxicity.

Other signs and symptoms can include aphasia, confusion, seizure, delirium, and cerebral edema. All patients receiving CAR T-cell should have a thorough baseline neurologic evaluation, and should be routinely assessed for neurologic signs and symptoms during treatment. Patients who exhibit these signs and symptoms should be evaluated for other potential causes of neurotoxicity.

“Antiseizure prophylaxis is becoming more common,” Ms Anderson said.

“Nursing assessments are really necessary for patients undergoing CAR-T—they need careful monitoring and daily lab tests during the high-risk acute toxicity periods. We are trying to identify risk factors for CRS so we can intervene earlier,” she noted.

Patients need to be educated about what to expect from CAR T-cell therapy so that they can recognize the signs and symptoms of potential toxicities. They should be aware that fever and infections are important concerns, and should have 24-hour access to a provider so that they can report emerging symptoms.

“There is still much we don’t know about CAR-T. The future is wide open. We need to be on top of toxicity management and long-term follow-up. Future studies will address new antigen targets, T-cell dosing strategies, optimal therapeutic timing, combinations of CAR-T with other therapies, and psychosocial impact,” Ms Anderson stated.

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Last modified: August 7, 2017