CAR T study finds decade-long lymphoma remissions in some patients

A long-running study of a CAR T-cell therapy found that some patients with B-cell lymphomas remained alive and free of relapse 10 years after a single infusion, according to researchers at the University of Pennsylvania. The findings add evidence that durable responses to CAR T treatment may amount to cures for a portion of patients, while underscoring that the therapy still fails many others.

The data, published in the New England Journal of Medicine, came from 38 patients in a Phase II clinical trial at Penn Medicine’s Abramson Cancer Center, according to the Perelman School of Medicine at the University of Pennsylvania. The group included 24 patients with large B-cell lymphoma and 14 with follicular lymphoma who received tisagenlecleucel, the CAR T-cell therapy developed by Carl June, MD, that later became the first CAR T treatment approved by the U.S. Food and Drug Administration.

After a median follow-up of 10 years, more than one-third of the large B-cell lymphoma patients and nearly half of the follicular lymphoma patients were alive without a lymphoma relapse, the Penn researchers reported. No patient in the analysis relapsed after 5.4 years, and most relapses happened during the first year after infusion.

Stephen J. Schuster, MD, senior author of the study and director of Penn’s Lymphoma Program, said oncologists use the word “cure” carefully but that he is increasingly confident CAR T-cell therapy can cure a meaningful number of patients with B-cell lymphomas. He also said the treatment does not work for everyone and that researchers are trying to understand why.

CAR T-cell therapy involves modifying a patient’s immune cells to recognize and attack cancer. In this study, patients whose responses lasted longer appeared to have higher levels of CAR T cells in their blood during the first two years after treatment, according to the Penn team. The researchers said persistence of those cells appeared to matter more than the size of the early post-infusion expansion.

Safety findings over 10 years

The trial enrolled patients with relapsed or refractory lymphoma, meaning their disease had returned after treatment or had stopped responding to therapy, according to the study team. At enrollment, patients had received a median of four prior treatments, including chemotherapy; some had also undergone autologous stem cell transplant.

The researchers said those earlier treatments can carry long-term risks, making it difficult to assign the cause of later health problems. Two of the 38 patients had ongoing grade 2 or 3 neutropenia, a low white blood cell count. The team reported no ongoing anemia or thrombocytopenia.

More than half of patients with a long-term response recovered normal B cells without recurrence of their B-cell lymphoma, according to the Penn researchers. The study investigators found no cases of secondary lymphoma linked to CAR T cells.

Nine patients developed a second primary cancer, the researchers reported. Those cases included acute myeloid leukemia in three patients, prostate cancer in two, lung cancer in two patients with a smoking history, melanoma in one and a skin-affecting form of T-cell lymphoma in one.

The 10-year rate of second primary cancers was higher in the study group than in comparable U.S. SEER data, according to the Penn team, but was consistent with other reports involving lymphoma patients treated with chemotherapy and autologous transplant.

Marco Ruella, MD, lead author and scientific director of Penn’s Lymphoma Program, said the decade-long remissions were encouraging. He said using CAR T-cell therapy earlier, before patients accumulate effects from repeated chemotherapy, may help extend its curative potential.

The research team said it is studying ways to improve CAR T-cell therapy, including whether the lymphodepleting chemotherapy patients currently receive before CAR T treatment is necessary.

This story draws on original reporting from Medical Xpress.