Clinical trial to test consolidated therapy to prevent relapse after CAR-T-cell therapy

When CAR-T-cell therapy works, the results can seem miraculous. Brian Hess, M.D., has seen a patient progress from being hunched over in a wheelchair, wracked with pain, to planning a five-month trip through southern Europe and Israel after going through CAR-T-cell therapy.

But CAR-T-cell therapy doesn’t work for everyone with lymphoma. For some, it doesn’t work at all. For others, it works well enough for a time. These patients go into partial remission after CAR-T-cell therapy or show what doctors call stable disease – cancer that hasn’t gotten worse but hasn’t gotten better, either.

Of the patients in partial remission or with stable disease, about two-thirds will relapse, said Hess, a physician scientist at MUSC Hollings Cancer Center. 

“Unfortunately, the prognosis for these patients that relapse after CAR-T is very poor,” he said. “There is a study coming out that showed that the median overall survival for patients relapsing after CAR-T is six months. So we're trying to prevent that relapse before it happens because their prognosis is so poor.”

Hess is now leading a national clinical trial to investigate whether particular drugs, individually or in combination, will prevent relapse in patients with large B-cell lymphoma who have partial remission or stable disease after CAR-T-cell therapy. The trial opened this month and enrolled its first patient last week.

"The two have been used in combination in a clinical trial in patients with already-relapsed disease, including patients relapsing after CAR-T, and the efficacy has been really, really promising. We're trying to prevent relapse in these patients by giving these drugs as ‘consolidation’ prior to relapse.”

Brian Hess, M.D.

People who enroll in the trial will receive polatuzumab vedotin and/or mosunetuzumab.

“Mosunetuzumab is a really exciting drug that is not yet approved for large cell lymphoma,” Hess said. “It probably will be in the next six months, but it won't be approved in this setting.”

The drug is a bispecific antibody, meaning it has two arms, each of which is primed to attach to a specific protein on the surface of a cell. One arm binds to a lymphoma cell while the other binds to a T-cell, a part of the body’s immune system. Bringing the two close together helps the T-cell to attack and kill the cancer cell.

“This therapy has been shown to be really successful in lymphoma patients, even in patients who have relapsed after CAR-T,” Hess said.

Polatuzumab vedotin, a monoclonal antibody combined with an anti-cancer drug, is already used in combination with chemotherapy drugs in some cases for people with large cell lymphoma but not in the particular instance that Hess is looking at.

"The two have been used in combination in a clinical trial in patients with already-relapsed disease, including patients relapsing after CAR-T, and the efficacy has been really, really promising,” he said. “We're trying to prevent relapse in these patients by giving these drugs as ‘consolidation’ prior to relapse.”

In those clinical trials of patients who have already relapsed, half went into complete remission. Hess hopes that the results will be even better in this trial because the patients will get the drugs before relapse and so will have fewer tumors and circulating cancer cells.

In addition, the trial will monitor participants’ minimal residual disease levels with an eye toward future clinical trials. This can be measured with a blood draw, but there isn’t enough information yet to know what to do with the results.

“We're hoping that something like minimal residual disease can be a really special, sensitive and specific test that will tell us at day 30 after CAR-T, or at a different time point, this patient is going to relapse; this patient is not going to relapse,” Hess said.

The trial is being run under the auspices of the SWOG Cancer Research Network, an alliance of researchers that encompasses more than 12,000 people at 1,000 hospitals and clinics worldwide. Hess expects the trial to be offered in about 40 locations.

He noted that he worked with dozens of people to get the trial approved by SWOG and the National Cancer Institute.

“It was just a giant effort, and I'm really proud of that,” he said. “And I think part of the reason I'm proud of it is because I really believe in this study – that patients like this should have this option, and I really am optimistic that these patients will do well.”

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