New Chemotherapy Alternative for Lymphoma

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Leo Gordon, MD, the Abby and John Friend Professor of Oncology Research, professor of Medicine in the Division of Hematology and Oncology, and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, was a co-author of the study published in The Lancet.

A new immunotherapy treatment for recurrent B-cell lymphoma was found to be safe in a trial of nearly 350 patients, according to a study published in The Lancet.

The therapy, which genetically modifies patient T-cells into aggressive cancer killers, could be a breakthrough for a cancer that has few other treatment options, according to Leo Gordon, MD, the Abby and John Friend Professor of Oncology Research, professor of Medicine in the Division of Hematology and Oncology and a co-author of the study.

“We are encouraged by the early results we saw, but we still have work to do to improve those outcomes,” said Gordon, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “What we have so far is not enough, but it is a start.”

B-cells are blood cells that make antibodies to fight bacteria and viruses. In B-cell lymphoma, the body produces too many abnormal B-cells which can spread to other parts of the body such as the lymph nodes, bone marrow or spleen.

Initial treatment is usually chemotherapy, but options for recurring disease are limited. Fewer than 50 percent of patients with multiply relapsed or chemotherapy-resistant B-cell lymphoma respond to treatment, according to Gordon, and overall survival is often less than six months.

“Patients with aggressive lymphoma who progress after multiple treatments have very poor outcomes,” Gordon said.

Chimeric antigen receptor (CAR-T) treatments are a possible solution to this problem. Clinicians collect T-cells from patients in a procedure called leukapoehresis that removes T-cells from the blood, and the cells are sent to a laboratory where new genes are inserted into the cells.

These genes cause the T-cells to recognize and attack a target — in this case, a particular protein on lymphoma cells. This process of manufacturing the cells can take several weeks, and afterwards the cells are infused back into the patient.

In the study, investigators obtained T-cells from 344 patients, 269 of whom received at least one dose of the modified T-cells. The treatment was well-tolerated: While many patients had side effects such as low neutrophil count or anemia, few had serious side effects.

Median survival among treated patients was extended to 18 months, and 73 percent of patients exhibited a response to the treatment, indicating the CAR-T cells were working.

These findings give investigators vital information about safety, including what side effects to expect and how to respond. Further trials treating B-cell lymphoma with CAR-T therapy are ongoing, and these results are an encouraging step for the therapy, Gordon said.

“This treatment has been used where more traditional treatments have failed, so the advantage is that CAR-T therapy works by a completely different mechanism than chemotherapy or radiation or surgery,” Gordon said. “In that sense CAR-T therapy represents a new step forward in the treatment of malignancy.”

This study was funded by Juno Therapeutics, a Bristol-Myers Squibb Company.