While chimeric antigen receptor (CAR) T-cell (CAR-T) therapies targeting the CD19 antigen have produced durable remissions, potentially severe toxicities, such as cytokine release syndrome and immune effector cell neurotoxicity syndrome, may limit their use. But, these severe reactions are often reversible.
Perhaps less discussed is what can happen when a patient is “waiting for CAR-T,” or during the period in which patients wait for their cells to be processed and engineered into adoptive cell therapies. This bridging period, as it is known, can leave patients extremely vulnerable.
“There is a 2-4 week period of cell processing and manufacturing and there is always a risk of progression during a time period of no treatment,” said Joshua Mansour, MD, a board-certified hematologist and oncologist in Stanford, California.
“In terms of bridging strategy, there are several different approaches that can be taken as one waits for the CAR T cells to be developed,” said Stephanie F. Williams, MD, division chief, adult blood and marrow transplant program, Spectrum Health, Grand Rapids, Michigan, in an interview with Cancer Therapy Advisor. “Many of the patients are refractory to chemotherapy, so different types of agents such as venetoclax or [immounomodulatory drugs] could be helpful. Radiation therapy is another option that can also be used as a bridging therapy.”
However, according to a recent retrospective review of adult patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL), chemotherapy may not be the best solution.
“Use of high- compared to low-intensity bridging was not associated with higher rates of successful CAR T cell infusion (63% vs 79%, P >.05) or a combined end point of CAR T-cell infusion or alternative therapy including transplant (80% vs 86%, P >.05),” the authors wrote in an abstract.
They defined bridging therapy as any therapy given from trial enrollment to cell infusion that could be classified as either high intensity (remission-inducing or myelosuppressive regimens, such as hyper-CVAD or high-dose cytarabine-based regimens) or low intensity, such as maintenance or less myelosuppressive regimens, including POMP (purinethol [6-mercaptopurine], oncovin, methotrexate, and prednisone), blinatumomab, and tyrosine kinase inhibitors).
“We’re still gathering more data on this early treatment of B-ALL on the success of CAR-T treatment. Although it’s currently approved in adults for B-ALL, in adult patients younger than 26 years old with refractory disease greater or equal to 2 relapses, continued studies and trials will help guide us toward determining if earlier implementation of CAR-T therapy as a treatment would be beneficial,” concluded Dr Mansour.
Perica K, Flynn J, Curran KJ, et al. Impact of bridging chemotherapy on clinical outcome of CD19 CAR T therapy in adult ALL. Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 2520.