What is the impact of bridging therapy on the outcomes of patients receiving CAR T Therapy?
Watch Dr. Michael Jain to find out.
Selecting Who Receives Bridging Chemo is Key
At the 2019 American Society of Hematology conference, Dr. Michael Jain, assistant member of Moffitt’s Blood and Marrow Transplant and Cellular Immunotherapy Department, presented new data that shows poorer outcome for patients who receive bridging therapy prior to CAR T-cell therapy.
Dr. Jain and his collaborators looked at the U.S. CAR T Lymphoma Consortium data to determine if administering a bridging therapy – radiation, chemotherapy, steroids or targeted therapy – could help patients in declining health who were waiting for their CAR T treatment to be scheduled. Physicians from this group of cancer treatment centers pool data and outcomes from their CAR T patient populations to ask questions that can help optimize care and administration of the therapy. To date, they have information on nearly 300 patients who received Yescarta after the therapy was approved and made available commercially.
The findings report that of the 298 patients included in the data set, 158 received some type of bridging therapy. Conversely, patients who did not require bridging therapy had excellent outcomes, with 80% of patients still alive one year after CAR T treatment.
“We found that overall response was worse for patients who received bridging therapy prior to CAR T-cell therapy,” said Dr. Jain. “This does not mean bridging therapy should be abandoned for this group of patients; however, doctors do need to be careful when selecting if and what bridging therapy a patient should receive before their CAR T infusion."
Chimeric Antigen Receptor T-cell Therapy, or CAR T for short, can provide good outcomes for patients with diffuse large B cell lymphoma (DLBCL) who have failed other therapies and/or have relapsed. More than 40% of patients who received Yecarta®, one of the two FDA-approved CAR T products for DLBCL, have seen durable responses. But for patients who have relapsed or are in declining health, there are some downsides to the therapy.
“Once we’ve collected the patient’s T cells and shipped them to the production facility, it can take up to three weeks to receive the re-engineered CAR T cells back from the manufacturer,” said Dr. Michael Jain. “Often a patient may need some type of intervention during that window of time to prevent further decline. There can also be severe toxicities once the therapy has been administered.”
Lymphoma patients receiving bridging therapy had poorer prognostic factors at baseline and after axi-cel infusion experienced decreased lymphoma-specific and overall survival compared with patients with no bridging. This inferior outcome raises the possibility that bridging therapy may identify a sub-group of lymphoma patients with a different biology, or alternatively, bridging therapy may have an effect on the host or the tumor microenvironment that may impact CAR-T efficacy. With or without bridging, 7% of patients in our series did not receive axi-cel due to lymphoma progression and/or death. In addition, there may have been patients where bridging prevented progression or death prior to axi-cel infusion. Prospective evaluation of different bridging strategies is warranted to determine if any can improve outcomes after axi-cel, and/or if they should be utilized only for patients requiring emergent disease control during the manufacture period.