CAR T-Cell Therapy Granted Priority Review for DLBCL

February 13, 2018

The US FDA has granted Priority Review designation for tisagenlecleucel (Kymriah) for treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for, or have relapsed after, ASCT.

The US Food and Drug Administration (FDA) has granted Priority Review designation for tisagenlecleucel (Kymriah), formerly known as CTL019, for treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or have relapsed after, autologous stem cell transplant.

Tisagenlecleucel is a one-time injection of chimeric antigen receptor (CAR) T cells manufactured for an individual patient using their own cells. The treatment was granted priority review based on results of the phase II JULIET trial, which was presented at the 59th American Society of Hematology Annual Meeting and Exposition.

The trial included 81 patients infused with tisagenlecleucel with 3 or more months of follow-up or earlier discontinuation. The overall response rate was 53% (P < .0001), with 40% of these patients achieving a complete response and 14% achieving partial response. At 6 months, the overall response rate was 37%, and 30% of responders had a complete response. Median duration of response was not yet reached. The relapse-free probability at 6 months after first response was 74%. Median overall survival was not reached.

“At the time of trial enrollment, these patients with DLBCL had been through multiple rounds of chemotherapy and many had unsuccessful stem cell transplants, leaving them with few options and a poor prognosis,” the study’s principal investigator Stephen J. Schuster, MD, said in a press release. “With tisagenlecleucel, we have been able to significantly increase their chance of achieving and maintaining a sustained response without stem cell transplant, demonstrating the therapy’s benefit in the treatment of this lethal blood cancer.” Dr. Schuster is the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research in the University of Pennsylvania’s Perelman School of Medicine and director of the Lymphoma Program at the Abramson Cancer Center.

More than half (58%) of treated patients in JULIET experienced cytokine release syndrome, which was a grade 3/4 event in about one-quarter of the patients. In addition, 21% of patients experienced any-grade neurologic events; 12% had grade 3/4 neurologic events, which were managed with supportive care.

Other CAR T-cell therapies approved in 2017 include tisagenlecleucel for the treatment of children and young adults up to 25 years of age with relapsed or refractory B-cell precursor acute lymphoblastic leukemia and axicabtagene ciloleucil (aci-cel; Yescarta) for adults with relapsed or refractory DLBCL.

CAR T-cell therapy was also named as the American Society of Clinical Oncology’s Advance of the Year in its Clinical Cancer Advances 2018: ASCO’s Annual Report on Progress Against Cancer.

“It is remarkable to see these decades of effort come together to create this whole new type of treatment, as well as other precision medicine approaches that offer hope to people with advanced cancer,” ASCO President Bruce E. Johnson, MD, said in a press release. “While we still have work to do to make these treatments accessible to patients everywhere and more tolerable, the successes of CAR T-cell therapy demonstrate the profound impact new treatments could make to markedly extend the lives of people with cancer.”