STEM CELL TRANSPLANT has been an established treatment for people with diffuse large B-cell lymphoma (DLBCL) since the 1990s. However, fewer people with DLBCL are receiving transplants as part of their cancer treatment since new therapeutic options for DLBCL have become available.

A registry maintained by the European Society for Blood and Marrow Transplantation shows that the number of people with DLBCL undergoing autologous stem cell transplant decreased from a peak in 2019 of 2,385 to 1,548 in 2022. Autologous transplants use the patient’s own stem cells.

During that same time, more people with DLBCL received a new option called chimeric antigen receptor (CAR) T-cell therapy. In CAR T-cell therapy, immune cells are collected from a patient’s blood and altered in a lab to attack cancer cells, before they are infused back into the patient.

There are currently three CAR T-cell therapies approved by the Food and Drug Administration (FDA) for DLBCL: Yescarta (axicabtagene ciloleucel) and Breyanzi (lisocabtagene maraleucel) are approved as third-line treatments, and Kymriah (tisagenlecleucel) is approved in the second line. Between 2019 and 2022, the number of people treated with CAR T-cell therapy rose from 537 to 809.

“This is not at all surprising given that CAR T-cell therapy has been FDA approved as a third- or later-line treatment for large B-cell lymphoma since 2017,” says Frederick Locke, a medical oncologist and translational researcher at Moffitt Cancer Center in Tampa, Florida.

“The decrease in the use of autologous stem cell transplant likely has to do with the knowledge that CAR T-cell therapy is potentially curative for patients, many of whom might not have been the best candidates for transplant,” Locke says.

Only a minority of people with DLBCL can receive autologous stem cell transplant, Locke explains. Transplant is used in patients who have relapsed or refractory DLBCL who have achieved either a partial or complete response to second-line chemotherapy.

Sunita Nasta, a medical oncologist at Penn Medicine’s Abramson Cancer Center in Philadelphia, illustrated eligibility and success of transplant with numbers.

“If you have 300 patients with large cell lymphoma at diagnosis, 200 of them will be cured with rituximab-containing regimens in the first line,” Nasta says of a monoclonal antibody drug used to treat blood cancers. “That leaves 100 patients who may need another therapy. Prior to five years ago, that therapy was autologous stem cell transplant.”

Of those 100 people, only half would be considered healthy and young enough to receive a stem cell transplant, Nasta estimates. Of those, just 25 would be eligible to receive a stem cell transplant because they had a partial or complete response to chemotherapy.

However, more patients, including those who are older, who have comorbidities or whose cancer is not responding to chemotherapy, would be eligible for CAR T-cell therapy. In addition, two recent clinical trials have demonstrated the benefits of CAR T-cell therapy in people with DLBCL. These include a trial that found people given CAR T-cell therapy in the second line of treatment went longer without cancer recurrence or symptoms than those who underwent stem cell transplant, and another study that found CAR T-cell therapy in that setting led to longer overall survival than stem cell transplant.

Still, CAR T-cell therapy has potential for side effects. “Although CAR T-cell therapy is generally better tolerated than autologous stem cell transplant, it is not an entirely benign therapy,” Locke says.

One of the most common side effects is called cytokine release syndrome, where the infused T cells flood the blood with cytokines, signaling proteins that control inflammation. This can result in high fever or rapid declines in blood pressure. Neurologic effects, such as confusion or impaired speech, can also occur as a result of CAR T-cell therapy.

Stem cell transplants can still be an option for certain patients, Locke says, for example, if a patient has already received second-line therapy and had a complete response.

“We know from historical data that if they have a complete response and go forward with high-dose chemotherapy and transplant that they have a high likelihood of doing well,” Locke says, adding that data have shown CAR T-cell therapy can also benefit people who have had a complete response.

To determine what treatment might be best, patients should ask their doctor about all available options, including clinical trials, Nasta says, even if the discussion includes the doctor telling the patient that a certain option is not the right one for them.