FDA Approves CAR-T Cell Therapy for Diffuse Large B-Cell Lymphoma

The Food and Drug Administration (FDA) approved Kymriah (tisagenlecleucel) — a CAR-T cell therapy – for the treatment of adult patients who have relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have relapsed or are ineligible for an autologous stem cell transplant (ASCT).

DLBCL is the most common form of non-Hodgkin lymphoma.

The approval follows promising findings from the multi-national phase 2 JULIET study, where Kymriah, formerly CTL019, had an overall response rate of 50 percent, with 32 percent of patients experiencing a complete response and 18 percent receiving a partial response. Median duration of response was not reached among the patients.

“We’re proud to have developed this therapy through all phases of development and clinical trials right here at Penn and in collaboration with Novartis,” said Carl June, M.D., the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center, in a statement.

The drug is the second to be approved for patients with DLBCL in more than three decades.

“The approval of Kymriah for patients with relapsed and refractory DLBCL is a major step forward to continue improving treatment outcomes for these patients. It is the second CAR-T cell to be approved, based on high response rates in patient populations with unmet medical needs,” Anas Younes, M.D., chief of the Lymphoma Service at Memorial Sloan Kettering (MSK) Cancer Center, said in an interview with CURE.

In the study, 77 percent of participants had stage 3 or 4 disease at baseline, and 47 percent previously received ASCT. Nearly all (95 percent) patients received at least two lines of prior antineoplastic therapy, with an average of three lines. Patients with prior ASCT and those with double-hit lymphoma, a subtype of DLBCL who typically have poor outcomes, had similar response rates.

Looking forward, Younes mentioned that CAR-T cell therapy will continue to move into the treatment landscape for hematologic malignancies, but more research is needed to determine which patients are best fit for the therapy. Younes also predicts that the price of the drug — which is currently very high – will decrease with time as more products become available on the market.

“Ongoing randomized trials are comparing CAR-T cell therapy to standard autologous stem cell transplant, and (those that) plan to move CAR-T cells to the frontline regimens in high-risk patients are underway. Long-term follow up will be needed to determine how many patients will be cured with this new therapy,” he said. “We also need to understand how to better manage the unique toxicities of these drugs.”

Side effects noted in the trial included cytokine release syndrome, neurological events, prolonged cytopenia, infections and febrile neutropenia.

“This is an exciting event — seeing this lifesaving therapy become available widely to a large patient population with an unmet medical need,” said Stephen J. Schuster, M.D., the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research and director of the Lymphoma Program at Penn’s Abramson Cancer Center, in a statement.

“Many lives may be saved.”