Should CAR T-Cell Therapy be the Standard Third Line Treatment for Non-Hodgkin Lymphoma?

Important Considerations

• A functional population of T-cells is necessary for CAR T-cell therapy, therefore multiple previous lines of treatment can reduce the effectiveness of the T-cell population
• The more treatments patients receive, the fewer normal T-cells remain, which may influence the efficacy of CAR T-cell therapy if needed as third or fourth line treatment
• Physicians need to think about second-line therapeutic sequences that preserve the immune system so CAR T-cell therapy is a viable option if needed

“If you don’t think of CAR T-cell therapy as a third line of therapy, you’re malpracticing,” Dr. Stephen Schuster, Penn Medicine hematologist/oncologist, tells SurvivorNet Connect. His concern is that, “It’s not yet gelled in the mind of all practicing oncologists that this is a reality for their patients.” Dr. Schuster is eager to raise awareness of CAR T-cell therapy because its success as third line therapy depends in large part on earlier therapeutic choices.

“We need healthy T-cells to do CAR T-cell therapy,” he explains. “And the problem is that the drugs used to kill malignant lymphocytes also kill normal T-cells.” The more cycles of chemotherapy a patient receives, the less and less efficacious the treatments become, and the fewer normal T-cells are left. The healthy cells can repopulate. But, the problem, Dr. Schuster says, is that if earlier therapy has been unsuccessful, the malignant cells repopulate as well, “and you may lose the race waiting for that.”

In order for CAR T-cell therapy to be available as an option for patients requiring third line treatment, physicians need to think about earlier therapeutic sequences that eradicate malignant lymphocytes but preserve the immune system. And patients need to be quickly directed to cancer centers that provide CAR T-cell therapy rather than having the disease held at bay with further therapies that weaken the immune system and threaten the success of T-cell based therapies. “You can’t just hammer away, hammer away, if a high-dose chemotherapy isn’t going to work from a prognostic standpoint in the second line,” says Dr. Schuster.

The ultimate message, says Dr. Schuster, is that there are great positives in first-line therapy, but when you get to the second line, “be cognizant of what you may lose with a chemotherapeutic approach. If a patient falls in a group that has a high probability of success, by all means use the chemotherapeutic approach. But if not, you should be immediately looking at other options.”