Antibody Pair Knocks Down High-risk Follicular Lymphoma

First trial of combination immunotherapy for this cancer shows surprisingly high response rate.

There’s no cure for follicular lymphoma. Patients diagnosed with this common form of non-Hodgkin lymphoma will live with the disease — either in remission or active treatment — for the rest of their lives.

For most, the cancer is slow-growing, or indolent, with very high survival rates. But for a subset of patients, their lymphoma can grow faster and outcomes may be worse.

A new combination of antibody therapies tested at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine is showing promise for this group of high-risk follicular lymphoma patients. An initial analysis of a clinical trial testing pairing the antibodies loncastuximab and rituximab found that 96% of high-risk patients had some response to treatment, while 85% had a complete response, meaning their cancer could no longer be detected by imaging.

The phase 2 clinical trial is led by Juan Alderuccio, M.D., a Sylvester hematologist and lymphoma specialist and associate professor of medicine at the Miller School, and has enrolled 33 follicular lymphoma patients at Sylvester out of a targeted 39 to date. But the results are so positive that Dr. Alderuccio and his team plan to expand the trial to enroll a total of 100 patients at Sylvester and at other cancer centers. Dr. Alderuccio presented the initial results of the trial today—analyzing 27 out of those 33 patients—at the American Society of Hematology’s annual meeting in San Diego.

Improved Outcomes for High-risk Patients

The trial follows on the heels of a smaller clinical trial that tested loncastuximab alone for patients with B-cell lymphomas including follicular lymphoma. That trial showed promising if less dramatic results—a complete response rate of around 65%. Loncastuximab alone has also proven to be effective in trials for other lymphomas, including diffuse large B-cell lymphoma, an aggressive blood cancer. There is also unpublished data from animal studies that hinted that this combination might work for follicular lymphoma, Dr. Alderuccio said.

Sylvester Comprehensive Cancer Center researcher  Juan Alderuccio
Juan Alderuccio, M.D.

Slightly more than half of the patients in the Sylvester trial had what’s called POD24, meaning they had progression of their disease within the first 24 months after initial treatment. For follicular lymphoma, this early progression is often a bad sign and is linked to higher risk of dying from the disease. The remaining patients were those deemed high-risk or with advanced disease by other clinical measures. 

“It’s a high-risk population and we’re trying to improve outcomes for these patients,” Dr. Alderuccio said.

Surprising Results

Dr. Alderuccio and his team were surprised by how good the results were. They designed their trial in stages, where they needed a certain number of complete responses in the first, smaller stage before progressing on to the second. They enrolled 19 patients for this first stage with the goal of seeing nine with complete responses—but those nine complete responses came after only the first 11 patients had been treated.

Those percentages have held up as they’ve moved to the second stage of the trial. Now, the team is looking for other centers to participate in the larger, multi-center trial that will test the two antibodies on 100 patients.

“It’s great that a program developed here at Sylvester is now capable of moving onto a multi-center study,” Alderuccio said. “If we’re able to observe the same good results in this larger group, hopefully this treatment will be available for every patient down the road.”

Tags: ASH2023, Dr. Juan Pablo Alderuccio, follicular lymphoma, lymphoma, Sylvester Comprehensive Cancer Center