Exploring Unanswered Questions on CAR-T Cell Therapy in Myeloma

The success of CAR- (chimeric antigen receptor) T cell therapy is causing landmark change in the way that patients with multiple myeloma are being treated, but more research needs to be done to better understand the role that these agents will play.

While one agent, bb2121 induced a 94 percent objective response rate and a 56 percent complete remission rate in patients with relapsed/refractory myeloma, there is still much more to be learned, according to Nina Shah, M.D.

“We’re really hoping that clinical trials will help us to understand where to position these drugs and also if we can do it earlier,” Shah, associate professor of medicine at the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, said in an interview with OncLive, a sister publication of CURE.

After seeing the success of bb2121, where about 90 percent of patients had minimal residual disease (MRD) negativity, even after a median of seven lines of prior treatment, Shah said that she is looking forward to opening several more clinical trials in this area.

Hopefully more trials will shed light on some currently unanswered questions about CAR-T cell therapy. For example, how do patients get over the resistance of CAR-T cell therapies?

“There are novel ways scientists everywhere, including at UCSF, are looking at trying to keep the CAR-T activated and keep them persistent,” Shah said. “This is so they could potentially turn them on and off so they can be effective, but not toxic.”

Research continues to chip away at these questions and more. One study being conducted at the University of Pennsylvania is testing dose-escalation, and has shown a 49 percent response rate. However, researchers are still deciding which chemotherapy they’re going to pair the CAR-T cell treatment with, and with which dose.

Meanwhile, a study in China tested the infusion of two different types of CAR-T cells. The duo was proven to be safe, though the trial was small — only including 10 patients – so larger studies still need to be done.

As studies continue to show promise, more talk is happening around moving these agents up in the treatment plan.

“I really hope that we can get CAR-T cells to mover sooner if, in fact, these data that we’re seeing hold up to be true for a long time,” Shah said.

However, she did note that the current frontline treatment for myeloma is keeping patients alive for years on end — and that should not be dismissed.

“Before we are able to move it upfront, we have to prove that it works,” Shah said, noting that there are proposals to use CAR-T cell therapy for high-risk patients, like those with plasma cell leukemia or a 17p deletion.

“If we can prove that we can extend the lives of these people or the disease-free time for these very high-risk patients, we start to believe that CAR-T cells could come sooner in lines of therapy, not when we’re having seven lines of refractory disease.”